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GHRP-6 The “Hunger Hormone” Explained

Vision

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(The information below was pulled from a very credible source that is pinpoint accurate with GHRP-2/6)

Ghrelin: The “Hunger Hormone” Explained

What is Ghrelin?

Ghrelin is a hormone produced in the gut. It is often termed the hunger hormone, and sometimes called lenomorelin.
It travels through your bloodstream and to your brain, where it tells your brain to become hungry and seek out food.
Ghrelin’s main function is to increase appetite. It makes you consume more food, take in more calories and store fat.

The graph below shows how rats injected with the hormone had a rapid increase in weight.

ghrelin-weight-gain-graph.jpg


In addition, it affects your sleep/wake cycle, reward-seeking behavior, taste sensation and carbohydrate metabolism.

This hormone is produced in your stomach and secreted when your stomach is empty. It enters the bloodstream and affects a part of the brain known as the hypothalamus,
which governs your hormones and appetite.

The higher your levels, the hungrier your get. The lower your levels, the more full you feel and the easier it is to eat fewer calories.
So if you want to lose weight, lowering your ghrelin levels can be beneficial.
Ghrelin may sound like a terrible, diet-wrecking hormone. However, in the past it played a role in survival by helping people maintain a healthy level of body fat.
These days, if you under-eat or struggle to gain weight, higher ghrelin levels may help you consume more food and calories per day.
Bottom Line: Ghrelin is a hormone that sends a signal to your brain to feel hungry. It plays a key role in regulating calorie intake and body fat levels.

Ghrelin levels typically rise before a meal, when your stomach is empty. Then they decrease shortly after, when your stomach is full.
While you might assume obese people have higher levels, they may just be more sensitive to its effects.
In fact, some research shows their levels are actually lower than in lean people.


Other research suggests that obese people may have an overly active ghrelin receptor, known as GHS-R,
which leads to increased calorie intake.

Yet regardless of how much body fat you have, ghrelin levels increase and make you hungry when you start a diet.
This is a natural response by your body, which tries to protect you from starvation.

During a diet, your appetite increases and your levels of the “fullness hormone” leptin go down. Your metabolic rate also tends to decrease significantly,
especially when you restrict calories for long periods of time.

For obvious reasons, these adaptations can make it significantly harder to lose weight and keep it off.
Your hormones and metabolism adjust to try to re-gain all the weight you lost.


Growth hormone releasing peptide 6, more commonly known as GHRP 6, is a popular peptide hormone. Basically, it is a hexapeptide composed of a 6 amino acids chain.
It is one of the numerous synthetic metenkephalin analogs which functions through incorporating manmade D amino acids. This peptide is a germ-free, non-pyrogenic,
lyophilized powder that is administered via the subcutaneous or intramuscular route. GHRP 6 is an effective human growth hormone secretagogue (GHS_.


Secretagogue is a name given to substances which prompts secretion of another substance. In this case, GHRP 6 produces growth hormones.
These have need widely used for a range of health promotion and clinical activities.
For example, GHRP 6 helps in the production of growth hormones the same way the body naturally produces its own growth hormone reserves.

It also provides similar functions on the skin, joints and muscle mass. Moreover, it has the ability to treat as well as undo the effects of deficient human growth hormone.

Authorised and legitimate use of hormone replacement therapy is an excellent method of ensuring a healthier and longer life coupled with improved general well-being.
GHRP 6 is one of those novel peptides that are able to promote increased energy and vigor. Despite this, it is important to know that GHRP 6 I distinctive from other growth hormone releasing peptides.
Note that it does not have any mechanism of action on the receptor of GHRH; rather, it mainly acts on the HGH secretagogoue receptor.
This HGH secretagogou receptor is also known as ghrelin receptor. Ghrelin is a very powerful substance that is able to stimulate the release of growth hormones from the pituitary gland.
It is also known as an important protector of neurons.


GHRP61.png

When should you use GHRP 6?

GHRP 6 is most commonly used for growth hormone replacement therapy. It is normally chosen by users because of the obvious cost advantage it offers.
Growth hormones are restricted by stringent laws hence, more and more people are turning in to GHRP 6 use. GHRP 6 is used to enhance skin and improve increase muscle gain and fat loss.

It is also used in conjunction with other anabolic steroids to promote greater synergistic effects which includes increased recovery from injuries.

What makes GHRP 6 a unique and useful peptide is that, you longer need to cycle it to receive all the benefits it offers.
You may use it for prolonged periods of time for any of the abovementioned reasons.
However, you must ensure to limit the dosage to the minimum suggested dosage range when you intent to use it on an ongoing basis.

Synergistic effects of GHRH and GHRH 6

GHRP 6 has the ability to promote increased production of growth hormones even when used alone.
A single dose of GHRP 6 is able to increase growth hormones in the body as compared to a growth hormone releasing hormone taken at the same time.
However, if you combine both GHRH and GHRP 6, only about a third or a half in as much as GHRP 6 is required for you to obtain the same amount of increase in growth hormone production. For this reason,
it is common for users to combine GHRH with GHRP. Users prefer to use CJC 1295 without DAC or Modified GRF 1-29 alongside GHRP 6.
GHRP 6: A ghrelin mimetic

All GHRPs, including GHRP 6 are ghrelin mimetics. Ghrelin is a hormone released by stomach cells in response to fasting.
Both ghrelin mimetics and ghrelin function through activating ghrelin receptors which are also known as growth hormone secretagogue receptor or GHS-R1a.
Increased levels of ghrelin improve growth hormone levels through stimulating ghrelin receptors in the pituitary gland.
Administration of any GHRP or GHRP 6 stimulates the release of growth hormone. It acts similarly with ghrelin.
However, the effect is greater. You may be able to achieve supraphysiological growth hormone levels through proper dosing of GHRP 6.
Benefits of ghrelin

Ghrelin has many functions in the body aside from stimulating the release of growth hormones in the body. It has the ability to protect the heart, increase appetite, decrease inflammation, promote healing, improve fat reduction as well as protect the cells from oxidative damage. It also has the ability to improve production of cortisol through increasing prolactin and ACTH.
Note however that ghrelin activity is comparable to what usually occurs during fasting.
Ghrelin has never been used to as a drug to enhance performance unlike that of GHRPs. Use of GHRPs as a performance-enhancing drug was documented and researched extensively.
In particular, GHRP 6 is effective in treating tendonitis which might be due to its ability to activate the ghrelin receptor.
Fasting is known to provide a range of beneficial effects in the body aside from fat loss. Similarly,
it may be quite true that elevation of ghrelin levels may provide health benefits such as healing and anti-inflammatory effect.
Hence, proper dosage and cycling of GHRP 6 to improve ghrelin levels may also provide the above benefits.


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DarkBeast

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Who doesnt like some GHRP!? :)
 

Vision

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Who doesnt like some GHRP!? :)

I love the stuff.. 10 tics before each meal, and I'm eating a massive platter.. the hunger pains are almost unreal!
 

Vision

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Sale is still going on boys!
 

Vision

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although the sale is over, you can still take advantage of this amazing product as a reasonable cost!
 

jozifp103

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although the sale is over, you can still take advantage of this amazing product as a reasonable cost!
That's it....i'm taking the dive and stocking up. I'm planning a 12 week cutter for summer then want to slowly ramp up into a nice heavy bulk. I'm gonna need that extra appetite. I wanna hit 250 again.
 

Vision

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That's it....i'm taking the dive and stocking up. I'm planning a 12 week cutter for summer then want to slowly ramp up into a nice heavy bulk. I'm gonna need that extra appetite. I wanna hit 250 again.
If you want an other appetite stimulate try Remeron..The effects are ferocious!!!!!

Mirtazapine, sold under the brand name Remeron among others, is an atypical antidepressant which is used primarily in the treatment of depression.[SUP][7][/SUP] In addition to its antidepressant properties, mirtazapine has anxiolytic, sedative, antiemetic, and appetite stimulant effects and is sometimes used in the treatment of anxiety disorders, insomnia, nausea and vomiting, and to produce weight gain when desirable.[SUP][7][/SUP][SUP][8][/SUP] It is taken by mouth.
The drug acts as an antagonist of certain adrenergic and serotonin receptors, and is also a strong antihistamine.[SUP][7][/SUP] It is sometimes described as a noradrenergic and specific serotonergic antidepressant (NaSSA),[SUP][7][/SUP]although the actual evidence in support of this label has been regarded as poor.[SUP][9][/SUP] Chemically, mirtazapine is a tetracyclic antidepressant (TeCA), with four interconnected rings of atoms, and is a relative of the TeCA mianserin(Tolvon).[SUP][10][/SUP][SUP][11][/SUP]
Mirtazapine was developed by Organon International in the Netherlands and was introduced in the United States in 1996.[SUP][4][/SUP] Its patent expired in 2004, so generic versions are available.[SUP][12]

[/SUP]

Approved and off-label[edit]

Mirtazapine's primary use is the treatment of major depressive disorder and other mood disorders.[SUP][13][/SUP][SUP][14][/SUP]
However, it has also been found useful in alleviating the following conditions and is sometimes prescribed off-label for their treatment:




Effectiveness and tolerability[edit]

In 2010 NICE published a guideline for treating depression that included a review of antidepressants. It recommended generic SSRIs as first line choices, as they are "equally effective as other antidepressants and have a favourable risk–benefit ratio."[SUP][29][/SUP] With respect to mirtazapine, it found: "There is no difference between mirtazapine and other antidepressants on any efficacy measure, although in terms of achieving remission mirtazapine appears to have a statistical though not clinical advantage. In addition, mirtazapine has a statistical advantage over SSRIs in terms of reducing symptoms of depression, but the difference is not clinically important. However, there is strong evidence that patients taking mirtazapine are less likely to leave treatment early because of side effects, although this is not the case for patients reporting side effects or leaving treatment early for any reason."[SUP][30][/SUP]
A 2011 Cochrane review that compared mirtazapine to other antidepressants, found that while it appears to have a faster onset in people for whom it works (measured at 2 weeks), it is about the same as other antidepressants at 6 weeks.[SUP][31][/SUP]
A 2012 review focused on antidepressants and sleep found that in many people with sleep disorders caused by depression, mirtazapine reduces the time it takes to fall asleep and increases the quality of sleep, but that in some people it can disturb sleep, causing restless leg syndrome in 8 to 28% of people, and in rare cases causes REM sleep behavior disorder.[SUP][32][/SUP]
A 2018 systematic review and network meta-analysis comparing the efficacy and acceptability of 21 antidepressant drugs showed mirtazapine to be one of the most effective antidepressants in head-to-head studies.[SUP][33][/SUP]
In general, all antidepressants, including mirtazapine, require at least a week for their therapeutic benefits on depressive and anxious symptoms to become apparent.[SUP][34][/SUP][SUP][35][/SUP]
Side effects[edit]

A 2011 Cochrane review found that compared with other antidepressants, it is more likely to cause weight gain and sleepiness, but it is less likely to cause tremor than tricyclic antidepressants, and less likely to cause nausea and sexual dysfunction than SSRIs.[SUP][31][/SUP]
Very common (≥10% incidence) adverse effects include constipation, dry mouth, sleepiness, increased appetite and weight gain.[SUP][4][/SUP][SUP][5][/SUP][SUP][6][/SUP][SUP][36][/SUP][SUP][37][/SUP][SUP][38][/SUP][SUP][39][/SUP][SUP][40][/SUP][SUP][41][/SUP]
Common (1–10% incidence) adverse effects include weakness, confusion, dizziness, peripheral edema, and negative lab results like elevated transaminases, elevated serum triglycerides, and elevated total cholesterol.[SUP][6][/SUP]
Mirtazapine is not considered to have a risk of many of the side effects often associated with other antidepressants like the SSRIs, and may actually improve certain ones when taken in conjunction with them.[SUP][7][/SUP][SUP][42][/SUP](Those adverse effects include decreased appetite, weight loss, insomnia, nausea and vomiting, diarrhoea, urinary retention, increased body temperature, excessive sweating, pupil dilation and sexual dysfunction.[SUP][7][/SUP][SUP][42][/SUP])
In general, some antidepressants, especially SSRIs, can paradoxically exacerbate some peoples' depression or anxiety or cause suicidal ideation.[SUP][43][/SUP] Despite its sedating action, mirtazapine is also believed to be capable of this, so in the United States and certain other countries, it carries a black box label warning of these potential effects.
A case report published in 2000 noted an instance in which mirtazapine counteracted the action of clonidine, causing a dangerous rise in blood pressure.[SUP][44][/SUP]
Discontinuation[edit]

Mirtazapine and other antidepressants may cause a discontinuation syndrome upon cessation.[SUP][7][/SUP][SUP][45][/SUP][SUP][46][/SUP] A gradual and slow reduction in dose is recommended to minimize discontinuation symptoms.[SUP][47][/SUP] Effects of sudden cessation of treatment with mirtazapine may include depression, anxiety, panic attacks, vertigo, restlessness, irritability, decreased appetite, insomnia, diarrhea, nausea, vomiting, flu-like symptoms such as allergies and pruritus, headaches and sometimes hypomania or mania.[SUP][45][/SUP][SUP][48][/SUP][SUP][49][/SUP][SUP][50][/SUP][SUP][51][/SUP]
Overdose[edit]

Mirtazapine is considered to be relatively safe in the event of an overdose,[SUP][35][/SUP] although it is considered slightly more toxic in overdose than most of the SSRIs (except citalopram).[SUP][52][/SUP] Unlike the tricyclic antidepressants, mirtazapine showed no significant cardiovascularadverse effects at 7 to 22 times the maximum recommended dose.[SUP][42][/SUP] Case reports of overdose with as much as 30 to 50 times the standard dose described the drug as relatively nontoxic, compared to tricyclic antidepressants.[SUP][53][/SUP][SUP][54][/SUP]
Twelve reported fatalities have been attributed to mirtazapine overdose.[SUP][55][/SUP][SUP][56][/SUP] The fatal toxicity index (deaths per million prescriptions) for mirtazapine is 3.1 (95% CI: 0.1 to 17.2). This is similar to that observed with SSRIs.[SUP][57][/SUP]
Interactions[edit]

Concurrent use with inhibitors or inducers of the cytochrome (CYP) P450 isoenzymes CYP1A2, CYP2D6, and/or CYP3A4 can result in altered concentrations of mirtazapine, as these are the main enzymes responsible for its metabolism.[SUP][3][/SUP][SUP][7][/SUP] As examples, fluoxetine and paroxetine, inhibitors of these enzymes, are known to modestly increase mirtazapine levels, while carbamazepine, an inducer, considerably decreases them.[SUP][3][/SUP] Liverand moderate renal impairment have been reported to decrease the oral clearance of mirtazapine by about 30%; severe renal impairment decreases it by 50%.[SUP][3][/SUP]
According to information from the manufacturers, mirtazapine should not be started within two weeks of any monoamine oxidase inhibitor (MAOI) usage; likewise, MAOIs should not be administered within two weeks of discontinuing mirtazapine.[SUP][58][/SUP] Mirtazapine in combination with an SSRI, SNRI, or TCA as an augmentation strategy is considered to be relatively safe and is often employed therapeutically,[SUP][42][/SUP] with a combination of venlafaxine and mirtazapine, sometimes referred to as "California rocket fuel".[SUP][59][/SUP][SUP][60][/SUP]
Pharmacology[edit]

Pharmacodynamics[edit]

See also: Pharmacology of antidepressants and Tetracyclic antidepressant § Pharmacology
SiteK[SUB]i[/SUB] (nM)SpeciesRef
SERT>10,000Human[SUP][62][/SUP][SUP][63][/SUP]
NET≥4,600Human[SUP][10][/SUP][SUP][62][/SUP]
DAT>10,000Human[SUP][62][/SUP][SUP][63][/SUP]
5-HT[SUB]1A[/SUB]3,330–5,010Human[SUP][63][/SUP][SUP][7][/SUP]
5-HT[SUB]1B[/SUB]3,534–12,600Human[SUP][63][/SUP][SUP][7][/SUP]
5-HT[SUB]1D[/SUB]794–5,010Human[SUP][63][/SUP][SUP][7][/SUP]
5-HT[SUB]1E[/SUB]728Human[SUP][63][/SUP]
5-HT[SUB]1F[/SUB]583Human[SUP][63][/SUP]
5-HT[SUB]2A[/SUB]6.3–69Human[SUP][7][/SUP][SUP][64][/SUP][SUP][63][/SUP]
5-HT[SUB]2B[/SUB]200Human[SUP][7][/SUP]
5-HT[SUB]2C[/SUB]8.9–39Human[SUP][64][/SUP][SUP][7][/SUP][SUP][63][/SUP]
5-HT[SUB]3[/SUB]7.9Human[SUP][7][/SUP]
5-HT[SUB]4L[/SUB]>10,000Human[SUP][63][/SUP]
5-HT[SUB]5A[/SUB]670Human[SUP][63][/SUP]
5-HT[SUB]6[/SUB]NDNDND[SUP][63][/SUP]
5-HT[SUB]7[/SUB]265Human[SUP][64][/SUP][SUP][63][/SUP]
α[SUB]1A[/SUB]316–1,815Human[SUP][63][/SUP][SUP][63][/SUP]
α[SUB]2A[/SUB]20Human[SUP][64][/SUP][SUP][63][/SUP]
α[SUB]2B[/SUB]88Human[SUP][63][/SUP]
α[SUB]2C[/SUB]18Human[SUP][64][/SUP][SUP][63][/SUP]
β>10,000Human[SUP][63][/SUP]
D[SUB]1[/SUB]4,167Rat[SUP][64][/SUP]
D[SUB]2[/SUB]>5,454Human[SUP][64][/SUP][SUP][63][/SUP]
D[SUB]3[/SUB]5,723Human[SUP][64][/SUP][SUP][63][/SUP]
D[SUB]4[/SUB]2,518Human[SUP][63][/SUP]
H[SUB]1[/SUB]0.14–1.6Human[SUP][65][/SUP][SUP][64][/SUP][SUP][7][/SUP][SUP][63][/SUP]
H[SUB]2[/SUB]>10,000Rat[SUP][66][/SUP][SUP][65][/SUP]
H[SUB]3[/SUB]83,200Human[SUP][65][/SUP]
H[SUB]4[/SUB]>100,000Human[SUP][65][/SUP]
mACh670Human[SUP][7][/SUP][SUP][10][/SUP]
VGSC6,905Rat[SUP][63][/SUP]
VDCC>10,000Rat[SUP][63][/SUP]
Values are K[SUB]i[/SUB] (nM). The smaller the value, the more strongly the drug binds to the site.

Mirtazapine has antihistamine, α[SUB]2[/SUB]-blocker, and antiserotonergic activity.[SUP][7][/SUP][SUP][67][/SUP] It is specifically a potent antagonist or inverse agonist of the α[SUB]2A[/SUB]-, α[SUB]2B[/SUB]-, and α[SUB]2C[/SUB]-adrenergic receptors, the serotonin 5-HT[SUB]2A[/SUB], 5-HT[SUB]2C[/SUB], and 5-HT[SUB]3[/SUB]receptors, and the histamine H[SUB]1[/SUB] receptor.[SUP][7][/SUP][SUP][67][/SUP] Unlike many other antidepressants, it does not inhibit the reuptake of serotonin, norepinephrine, or dopamine,[SUP][7][/SUP][SUP][67][/SUP] nor does it inhibit monoamine oxidase.[SUP][68][/SUP] Similarly, mirtazapine has weak or no activity as an anticholinergic or blocker of sodium or calcium channels, in contrast to most TCAs.[SUP][7][/SUP][SUP][67][/SUP][SUP][63][/SUP] In accordance, it has better tolerability and low toxicity in overdose.[SUP][7][/SUP][SUP][69][/SUP] As an H[SUB]1[/SUB]receptor antagonist, mirtazapine is extremely potent, and is in fact the most potent of all the TCAs and TeCAs.[SUP][10][/SUP][SUP][70][/SUP][SUP][71][/SUP] Antagonism of the H[SUB]1[/SUB] receptor is by far the strongest activity of mirtazapine, with the drug acting as a selective H[SUB]1[/SUB]receptor antagonist at low concentrations.[SUP][7][/SUP][SUP][63][/SUP]
The (S)-(+) enantiomer of mirtazapine is responsible for antagonism of the serotonin 5-HT[SUB]2A[/SUB] and 5-HT[SUB]2C[/SUB] receptors,[SUP][11][/SUP] while the (R)-(–) enantiomer is responsible for antagonism of the 5-HT[SUB]3[/SUB] receptor.[SUP][11][/SUP] Both enantiomers are involved in antagonism of the H[SUB]1[/SUB] and α[SUB]2[/SUB]-adrenergic receptors,[SUP][11][/SUP][SUP][5][/SUP] although the (S)-(+) enantiomer is the stronger antihistamine.[SUP][72][/SUP]
Although not clinically relevant, mirtazapine has been found to act as a partial agonist of the κ-opioid receptor at high concentrations (EC[SUB]50[/SUB] = 7.2 μM).[SUP][73][/SUP]
α[SUB]2[/SUB]-Adrenergic receptor[edit]

Antagonism of the α[SUB]2[/SUB]-adrenergic receptors, which function largely as inhibitory autoreceptors and heteroreceptors, enhances adrenergic and serotonergic neurotransmission, notably central 5-HT[SUB]1A[/SUB] receptor mediated transmission in the dorsal raphe nucleus and hippocampus; hence, mirtazapine's classification as a NaSSA. Indirect α[SUB]1[/SUB] adrenoceptor-mediated enhancement of serotonin cell firing and direct blockade of inhibitory α[SUB]2[/SUB]heteroreceptors located on serotonin terminals are held responsible for the increase in extracellular serotonin.[SUP][7][/SUP][SUP][13][/SUP][SUP][74][/SUP][SUP][75][/SUP][SUP][76][/SUP] Because of this, mirtazapine has been said to be a functional "indirect agonist" of the 5-HT[SUB]1A[/SUB]receptor.[SUP][75][/SUP] Increased activation of the central 5-HT[SUB]1A[/SUB] receptor is thought to be a major mediator of efficacy of most antidepressant drugs.[SUP][77][/SUP]
5-HT[SUB]2[/SUB] and 5-HT[SUB]3[/SUB] receptors[edit]

Antagonism of the 5-HT[SUB]2[/SUB] subfamily of receptors and inverse agonism of the 5-HT[SUB]2C[/SUB] receptor appears to be in part responsible for mirtazapine's efficacy in the treatment of depressive states.[SUP][78][/SUP][SUP][79][/SUP] Mirtazapine increases dopamine release in the prefrontal cortex.[SUP][80][/SUP][SUP][81][/SUP] Accordingly, it was shown that by blocking the α[SUB]2[/SUB]-adrenergic receptors and 5-HT[SUB]2C[/SUB] receptors mirtazapine disinhibited dopamine and norepinephrine activity in these areas in rats.[SUP][82][/SUP] In addition, mirtazapine's antagonism of 5-HT[SUB]2A[/SUB] receptors has beneficial effects on anxiety, sleep and appetite, as well as sexual function regarding the latter receptor.[SUP][7][/SUP][SUP][42][/SUP] Mirtazapine has been shown to lower drug seeking behaviour in various human and animal studies.[SUP][83][/SUP][SUP][84][/SUP][SUP][85][/SUP] It is also being investigated in substance abuse disorders to reduce withdrawal effects and improve remission rates.[SUP][83][/SUP][SUP][86][/SUP][SUP][87][/SUP][SUP][88][/SUP]
Antagonism of the 5-HT[SUB]3[/SUB] receptor, an action mirtazapine shares with the approved antiemetic ondansetron, significantly improves pre-existing symptoms of nausea, vomiting, diarrhea, and irritable bowel syndrome in afflicted individuals.[SUP][89][/SUP] Mirtazapine may be used as an inexpensive antiemetic alternative to ondansetron.[SUP][24][/SUP] Blockade of the 5-HT[SUB]3[/SUB] receptors has also shown to improve anxiety and to be effective in the treatment of drug addiction in several studies.[SUP][90][/SUP] In conjunction with substance abuse counseling, mirtazapine has been investigated for the purpose of reducing methamphetamine use in dependent individuals with success.[SUP][84][/SUP] In contrast to mirtazapine, the SSRIs, SNRIs, MAOIs, and some TCAs increase the general activity of the 5-HT[SUB]2A[/SUB], 5-HT[SUB]2C[/SUB], and 5-HT[SUB]3[/SUB] receptors leading to a host of negative changes and side effects, the most prominent of which including anorexia, insomnia, sexual dysfunction (loss of libido and anorgasmia), nausea, and diarrhea, among others. As a result, it is often combined with these drugs to reduce their side-effect profile and to produce a stronger antidepressant effect.[SUP][42][/SUP][SUP][91][/SUP]
Mirtazapine does not have serotonergic activity and does not cause serotonergic side effects or serotonin syndrome.[SUP][9][/SUP][SUP][92][/SUP] This is in accordance with the fact that it is not a serotonin reuptake inhibitor or MAOI, nor a serotonin receptor agonist.[SUP][9][/SUP][SUP][92][/SUP] There are no reports of serotonin syndrome in association with mirtazapine alone, and mirtazapine has not been found to cause serotonin syndrome in overdose.[SUP][9][/SUP][SUP][92][/SUP][SUP][93][/SUP] However, there are a handful of case reports of serotonin syndrome occurring with mirtazapine in combination with serotonergic drugs like SSRIs, although such reports are unusual, very rare, and do not necessarily implicate mirtazapine as causative.[SUP][9][/SUP][SUP][94][/SUP][SUP][95][/SUP][SUP][96][/SUP][SUP][97][/SUP][SUP][98][/SUP] The addition of mirtazapine to an MAOI does not cause serotonin syndrome, and has been considered to be a safe combination.[SUP][9][/SUP][SUP][92][/SUP] Moreover, mirtazapine may actually be useful in the treatment of serotonin syndrome, with at least one publication finding it to be effective in resolving the syndrome.[SUP][9][/SUP][SUP][99][/SUP][SUP][100][/SUP] This is in accordance with the fact that the 5-HT[SUB]2A[/SUB] receptor is the predominant serotonin receptor thought to be involved in the pathophysiology of serotonin syndrome (with the 5-HT[SUB]1A[/SUB] receptor seeming to be protective).[SUP][9][/SUP][SUP][92][/SUP] Mirtazapine is a potent 5-HT[SUB]2A[/SUB] receptor antagonist, and cyproheptadine, a drug that shares this property, mediates recovery from serotonin syndrome and is well-established clinically as an antidote against it.[SUP][9][/SUP][SUP][101][/SUP]
H[SUB]1[/SUB] receptor[edit]

Mirtazapine is a very strong H[SUB]1[/SUB] receptor inverse agonist and, as a result, it can cause powerful sedative and hypnotic effects.[SUP][7][/SUP] A single 15 mg dose of mirtazapine to healthy volunteers has been found to result in over 80% occupancy of the H[SUB]1[/SUB] receptor and to induce intense sleepiness.[SUP][72][/SUP] After a short period of chronic treatment, however, the H[SUB]1[/SUB] receptor tends to desensitize and the antihistamine effects become more tolerable. Many patients may also dose at night to avoid the effects, and this appears to be an effective strategy for combating them. Blockade of the H[SUB]1[/SUB] receptor may improve pre-existing allergies, pruritus, nausea, and insomnia in afflicted individuals. It may also contribute to weight gain, however. In contrast to the H[SUB]1[/SUB] receptor, mirtazapine has only low affinity for the muscarinic acetylcholine receptors, although anticholinergic side effects like dry mouth, constipation, and mydriasis are still sometimes seen in clinical practice.[SUP][102][/SUP]
Pharmacokinetics[edit]

The oral bioavailability of mirtazapine is about 50%. It is found mostly bound to plasma proteins, about 85%. It is metabolized primarily in the liver by demethylation and hydroxylation via cytochrome P450 enzymes. One of its major metabolites is desmethylmirtazapine. The overall elimination half-life is 20–40 hours. About 15% is eliminated in feces and 75% in urine.[SUP][103][/SUP][SUP]:430[/SUP]
History[edit]

Mirtazapine was first synthesized at Organon and published in 1989, was first approved for use in major depressive disorder in the Netherlands in 1994, and was introduced in the United States in 1996 under the brand name Remeron.[SUP][103][/SUP][SUP]:429[/SUP][SUP][104][/SUP][SUP][105][/SUP]
Society and culture[edit]


A 15 mg tablet of generic mirtazapine.​

Generic names[edit]

Mirtazapine is the English and French generic name of the drug and its INN, USAN, USP, BAN, DCF, and JAN.[SUP][1][/SUP][SUP][2][/SUP][SUP][106][/SUP] Its generic name in Spanish is mirtazapina, in German is Mirtazapin, and in Latin is mirtazapinum.[SUP][1][/SUP][SUP][2][/SUP]
Brand names[edit]

Mirtazapine is marketed under many brand names worldwide, including Adco-Mirteron, Afloyan, Amirel, Arintapin Smelt, Avanza, Azapin, Beron, Bilanz, Calixta, Ciblex, Combar, Comenter, Depreram, Divaril, Esprital, Maz, Menelat, Mepirzapine, Merdaten, Meronin, Mi Er Ning, Milivin, Minelza, Minivane, Mirastad, Mirazep, Miro, Miron, Mirrador, Mirt, Mirta, Mirtabene, Mirtadepi, Mirtagamma, Mirtagen, Mirtalan, Mirtamor, Mirtamylan, Mirtan, Mirtaneo, Mirtapax, Mirtapil, Mirtapine, Mirtaron, Mirtastad, Mirtax, Mirtaz, Mirtazap, Mirtazapin, Mirtazapina, Mirtazapine, Mirtazapinum, Mirtazelon, Mirtazon, Mirtazonal, Mirtel, Mirtimash, Mirtin, Mirtine, Mirzapine, Mirzaten, Mirzest, Mitaprex, Mitaxind, Mitocent, Mitrazin, Mizapin, Motofen, Mytra, Norset, Noxibel, Pharmataz, Promyrtil, Ramure, Redepra, Reflex, Remergil, Remergon, Remeron, Remirta, Rexer, Saxib, Sinmaron, Smilon, Tazepin, Tazimed, Tetrazic, Tifona, U-Mirtaron, U-zepine, Valdren, Vastat, Velorin, Yarocen, Zania, Zapex, Zestat, Zismirt, Zispin, Zuleptan, and Zulin.[SUP][2][/SUP]
Chemistry[edit]

Mirtazapine is a tetracyclic piperazinoazepine; mianserin was developed by the same team of organic chemists and mirtazapine differs from it via addition of a nitrogen atom in one of the rings.[SUP][103][/SUP][SUP]:429[/SUP][SUP][107][/SUP][SUP][108][/SUP] It is a racemic mixture of enantiomers. The (S)-(+)-enantiomer is known as esmirtazapine.
Analogues of mirtazapine include mianserin, setiptiline, and aptazapine.
Synthesis[edit]

A chemical synthesis of mirtazapine has been published.[SUP][109][/SUP]
Research[edit]

The use of mirtazapine has been explored in several additional conditions:



Veterinary use[edit]

Mirtazapine is sometimes prescribed as an appetite stimulant for cats or dogs experiencing anorexia due to medical conditions such as chronic kidney disease. It is especially useful for treating combined poor appetite and nausea in cats and dogs.[SUP][123][/SUP][SUP][124][/SUP]
 

jozifp103

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If you want an other appetite stimulate try Remeron..The effects are ferocious!!!!!

Mirtazapine, sold under the brand name Remeron among others, is an atypical antidepressant which is used primarily in the treatment of depression.[SUP][7][/SUP] In addition to its antidepressant properties, mirtazapine has anxiolytic, sedative, antiemetic, and appetite stimulant effects and is sometimes used in the treatment of anxiety disorders, insomnia, nausea and vomiting, and to produce weight gain when desirable.[SUP][7][/SUP][SUP][8][/SUP] It is taken by mouth.
The drug acts as an antagonist of certain adrenergic and serotonin receptors, and is also a strong antihistamine.[SUP][7][/SUP] It is sometimes described as a noradrenergic and specific serotonergic antidepressant (NaSSA),[SUP][7][/SUP]although the actual evidence in support of this label has been regarded as poor.[SUP][9][/SUP] Chemically, mirtazapine is a tetracyclic antidepressant (TeCA), with four interconnected rings of atoms, and is a relative of the TeCA mianserin(Tolvon).[SUP][10][/SUP][SUP][11][/SUP]
Mirtazapine was developed by Organon International in the Netherlands and was introduced in the United States in 1996.[SUP][4][/SUP] Its patent expired in 2004, so generic versions are available.[SUP][12]

[/SUP]

Approved and off-label[edit]

Mirtazapine's primary use is the treatment of major depressive disorder and other mood disorders.[SUP][13][/SUP][SUP][14][/SUP]
However, it has also been found useful in alleviating the following conditions and is sometimes prescribed off-label for their treatment:




Effectiveness and tolerability[edit]

In 2010 NICE published a guideline for treating depression that included a review of antidepressants. It recommended generic SSRIs as first line choices, as they are "equally effective as other antidepressants and have a favourable risk–benefit ratio."[SUP][29][/SUP] With respect to mirtazapine, it found: "There is no difference between mirtazapine and other antidepressants on any efficacy measure, although in terms of achieving remission mirtazapine appears to have a statistical though not clinical advantage. In addition, mirtazapine has a statistical advantage over SSRIs in terms of reducing symptoms of depression, but the difference is not clinically important. However, there is strong evidence that patients taking mirtazapine are less likely to leave treatment early because of side effects, although this is not the case for patients reporting side effects or leaving treatment early for any reason."[SUP][30][/SUP]
A 2011 Cochrane review that compared mirtazapine to other antidepressants, found that while it appears to have a faster onset in people for whom it works (measured at 2 weeks), it is about the same as other antidepressants at 6 weeks.[SUP][31][/SUP]
A 2012 review focused on antidepressants and sleep found that in many people with sleep disorders caused by depression, mirtazapine reduces the time it takes to fall asleep and increases the quality of sleep, but that in some people it can disturb sleep, causing restless leg syndrome in 8 to 28% of people, and in rare cases causes REM sleep behavior disorder.[SUP][32][/SUP]
A 2018 systematic review and network meta-analysis comparing the efficacy and acceptability of 21 antidepressant drugs showed mirtazapine to be one of the most effective antidepressants in head-to-head studies.[SUP][33][/SUP]
In general, all antidepressants, including mirtazapine, require at least a week for their therapeutic benefits on depressive and anxious symptoms to become apparent.[SUP][34][/SUP][SUP][35][/SUP]
Side effects[edit]

A 2011 Cochrane review found that compared with other antidepressants, it is more likely to cause weight gain and sleepiness, but it is less likely to cause tremor than tricyclic antidepressants, and less likely to cause nausea and sexual dysfunction than SSRIs.[SUP][31][/SUP]
Very common (≥10% incidence) adverse effects include constipation, dry mouth, sleepiness, increased appetite and weight gain.[SUP][4][/SUP][SUP][5][/SUP][SUP][6][/SUP][SUP][36][/SUP][SUP][37][/SUP][SUP][38][/SUP][SUP][39][/SUP][SUP][40][/SUP][SUP][41][/SUP]
Common (1–10% incidence) adverse effects include weakness, confusion, dizziness, peripheral edema, and negative lab results like elevated transaminases, elevated serum triglycerides, and elevated total cholesterol.[SUP][6][/SUP]
Mirtazapine is not considered to have a risk of many of the side effects often associated with other antidepressants like the SSRIs, and may actually improve certain ones when taken in conjunction with them.[SUP][7][/SUP][SUP][42][/SUP](Those adverse effects include decreased appetite, weight loss, insomnia, nausea and vomiting, diarrhoea, urinary retention, increased body temperature, excessive sweating, pupil dilation and sexual dysfunction.[SUP][7][/SUP][SUP][42][/SUP])
In general, some antidepressants, especially SSRIs, can paradoxically exacerbate some peoples' depression or anxiety or cause suicidal ideation.[SUP][43][/SUP] Despite its sedating action, mirtazapine is also believed to be capable of this, so in the United States and certain other countries, it carries a black box label warning of these potential effects.
A case report published in 2000 noted an instance in which mirtazapine counteracted the action of clonidine, causing a dangerous rise in blood pressure.[SUP][44][/SUP]
Discontinuation[edit]

Mirtazapine and other antidepressants may cause a discontinuation syndrome upon cessation.[SUP][7][/SUP][SUP][45][/SUP][SUP][46][/SUP] A gradual and slow reduction in dose is recommended to minimize discontinuation symptoms.[SUP][47][/SUP] Effects of sudden cessation of treatment with mirtazapine may include depression, anxiety, panic attacks, vertigo, restlessness, irritability, decreased appetite, insomnia, diarrhea, nausea, vomiting, flu-like symptoms such as allergies and pruritus, headaches and sometimes hypomania or mania.[SUP][45][/SUP][SUP][48][/SUP][SUP][49][/SUP][SUP][50][/SUP][SUP][51][/SUP]
Overdose[edit]

Mirtazapine is considered to be relatively safe in the event of an overdose,[SUP][35][/SUP] although it is considered slightly more toxic in overdose than most of the SSRIs (except citalopram).[SUP][52][/SUP] Unlike the tricyclic antidepressants, mirtazapine showed no significant cardiovascularadverse effects at 7 to 22 times the maximum recommended dose.[SUP][42][/SUP] Case reports of overdose with as much as 30 to 50 times the standard dose described the drug as relatively nontoxic, compared to tricyclic antidepressants.[SUP][53][/SUP][SUP][54][/SUP]
Twelve reported fatalities have been attributed to mirtazapine overdose.[SUP][55][/SUP][SUP][56][/SUP] The fatal toxicity index (deaths per million prescriptions) for mirtazapine is 3.1 (95% CI: 0.1 to 17.2). This is similar to that observed with SSRIs.[SUP][57][/SUP]
Interactions[edit]

Concurrent use with inhibitors or inducers of the cytochrome (CYP) P450 isoenzymes CYP1A2, CYP2D6, and/or CYP3A4 can result in altered concentrations of mirtazapine, as these are the main enzymes responsible for its metabolism.[SUP][3][/SUP][SUP][7][/SUP] As examples, fluoxetine and paroxetine, inhibitors of these enzymes, are known to modestly increase mirtazapine levels, while carbamazepine, an inducer, considerably decreases them.[SUP][3][/SUP] Liverand moderate renal impairment have been reported to decrease the oral clearance of mirtazapine by about 30%; severe renal impairment decreases it by 50%.[SUP][3][/SUP]
According to information from the manufacturers, mirtazapine should not be started within two weeks of any monoamine oxidase inhibitor (MAOI) usage; likewise, MAOIs should not be administered within two weeks of discontinuing mirtazapine.[SUP][58][/SUP] Mirtazapine in combination with an SSRI, SNRI, or TCA as an augmentation strategy is considered to be relatively safe and is often employed therapeutically,[SUP][42][/SUP] with a combination of venlafaxine and mirtazapine, sometimes referred to as "California rocket fuel".[SUP][59][/SUP][SUP][60][/SUP]
Pharmacology[edit]

Pharmacodynamics[edit]

See also: Pharmacology of antidepressants and Tetracyclic antidepressant § Pharmacology
SiteK[SUB]i[/SUB] (nM)SpeciesRef
SERT>10,000Human[SUP][62][/SUP][SUP][63][/SUP]
NET≥4,600Human[SUP][10][/SUP][SUP][62][/SUP]
DAT>10,000Human[SUP][62][/SUP][SUP][63][/SUP]
5-HT[SUB]1A[/SUB]3,330–5,010Human[SUP][63][/SUP][SUP][7][/SUP]
5-HT[SUB]1B[/SUB]3,534–12,600Human[SUP][63][/SUP][SUP][7][/SUP]
5-HT[SUB]1D[/SUB]794–5,010Human[SUP][63][/SUP][SUP][7][/SUP]
5-HT[SUB]1E[/SUB]728Human[SUP][63][/SUP]
5-HT[SUB]1F[/SUB]583Human[SUP][63][/SUP]
5-HT[SUB]2A[/SUB]6.3–69Human[SUP][7][/SUP][SUP][64][/SUP][SUP][63][/SUP]
5-HT[SUB]2B[/SUB]200Human[SUP][7][/SUP]
5-HT[SUB]2C[/SUB]8.9–39Human[SUP][64][/SUP][SUP][7][/SUP][SUP][63][/SUP]
5-HT[SUB]3[/SUB]7.9Human[SUP][7][/SUP]
5-HT[SUB]4L[/SUB]>10,000Human[SUP][63][/SUP]
5-HT[SUB]5A[/SUB]670Human[SUP][63][/SUP]
5-HT[SUB]6[/SUB]NDNDND[SUP][63][/SUP]
5-HT[SUB]7[/SUB]265Human[SUP][64][/SUP][SUP][63][/SUP]
α[SUB]1A[/SUB]316–1,815Human[SUP][63][/SUP][SUP][63][/SUP]
α[SUB]2A[/SUB]20Human[SUP][64][/SUP][SUP][63][/SUP]
α[SUB]2B[/SUB]88Human[SUP][63][/SUP]
α[SUB]2C[/SUB]18Human[SUP][64][/SUP][SUP][63][/SUP]
β>10,000Human[SUP][63][/SUP]
D[SUB]1[/SUB]4,167Rat[SUP][64][/SUP]
D[SUB]2[/SUB]>5,454Human[SUP][64][/SUP][SUP][63][/SUP]
D[SUB]3[/SUB]5,723Human[SUP][64][/SUP][SUP][63][/SUP]
D[SUB]4[/SUB]2,518Human[SUP][63][/SUP]
H[SUB]1[/SUB]0.14–1.6Human[SUP][65][/SUP][SUP][64][/SUP][SUP][7][/SUP][SUP][63][/SUP]
H[SUB]2[/SUB]>10,000Rat[SUP][66][/SUP][SUP][65][/SUP]
H[SUB]3[/SUB]83,200Human[SUP][65][/SUP]
H[SUB]4[/SUB]>100,000Human[SUP][65][/SUP]
mACh670Human[SUP][7][/SUP][SUP][10][/SUP]
VGSC6,905Rat[SUP][63][/SUP]
VDCC>10,000Rat[SUP][63][/SUP]
Values are K[SUB]i[/SUB] (nM). The smaller the value, the more strongly the drug binds to the site.

Mirtazapine has antihistamine, α[SUB]2[/SUB]-blocker, and antiserotonergic activity.[SUP][7][/SUP][SUP][67][/SUP] It is specifically a potent antagonist or inverse agonist of the α[SUB]2A[/SUB]-, α[SUB]2B[/SUB]-, and α[SUB]2C[/SUB]-adrenergic receptors, the serotonin 5-HT[SUB]2A[/SUB], 5-HT[SUB]2C[/SUB], and 5-HT[SUB]3[/SUB]receptors, and the histamine H[SUB]1[/SUB] receptor.[SUP][7][/SUP][SUP][67][/SUP] Unlike many other antidepressants, it does not inhibit the reuptake of serotonin, norepinephrine, or dopamine,[SUP][7][/SUP][SUP][67][/SUP] nor does it inhibit monoamine oxidase.[SUP][68][/SUP] Similarly, mirtazapine has weak or no activity as an anticholinergic or blocker of sodium or calcium channels, in contrast to most TCAs.[SUP][7][/SUP][SUP][67][/SUP][SUP][63][/SUP] In accordance, it has better tolerability and low toxicity in overdose.[SUP][7][/SUP][SUP][69][/SUP] As an H[SUB]1[/SUB]receptor antagonist, mirtazapine is extremely potent, and is in fact the most potent of all the TCAs and TeCAs.[SUP][10][/SUP][SUP][70][/SUP][SUP][71][/SUP] Antagonism of the H[SUB]1[/SUB] receptor is by far the strongest activity of mirtazapine, with the drug acting as a selective H[SUB]1[/SUB]receptor antagonist at low concentrations.[SUP][7][/SUP][SUP][63][/SUP]
The (S)-(+) enantiomer of mirtazapine is responsible for antagonism of the serotonin 5-HT[SUB]2A[/SUB] and 5-HT[SUB]2C[/SUB] receptors,[SUP][11][/SUP] while the (R)-(–) enantiomer is responsible for antagonism of the 5-HT[SUB]3[/SUB] receptor.[SUP][11][/SUP] Both enantiomers are involved in antagonism of the H[SUB]1[/SUB] and α[SUB]2[/SUB]-adrenergic receptors,[SUP][11][/SUP][SUP][5][/SUP] although the (S)-(+) enantiomer is the stronger antihistamine.[SUP][72][/SUP]
Although not clinically relevant, mirtazapine has been found to act as a partial agonist of the κ-opioid receptor at high concentrations (EC[SUB]50[/SUB] = 7.2 μM).[SUP][73][/SUP]
α[SUB]2[/SUB]-Adrenergic receptor[edit]

Antagonism of the α[SUB]2[/SUB]-adrenergic receptors, which function largely as inhibitory autoreceptors and heteroreceptors, enhances adrenergic and serotonergic neurotransmission, notably central 5-HT[SUB]1A[/SUB] receptor mediated transmission in the dorsal raphe nucleus and hippocampus; hence, mirtazapine's classification as a NaSSA. Indirect α[SUB]1[/SUB] adrenoceptor-mediated enhancement of serotonin cell firing and direct blockade of inhibitory α[SUB]2[/SUB]heteroreceptors located on serotonin terminals are held responsible for the increase in extracellular serotonin.[SUP][7][/SUP][SUP][13][/SUP][SUP][74][/SUP][SUP][75][/SUP][SUP][76][/SUP] Because of this, mirtazapine has been said to be a functional "indirect agonist" of the 5-HT[SUB]1A[/SUB]receptor.[SUP][75][/SUP] Increased activation of the central 5-HT[SUB]1A[/SUB] receptor is thought to be a major mediator of efficacy of most antidepressant drugs.[SUP][77][/SUP]
5-HT[SUB]2[/SUB] and 5-HT[SUB]3[/SUB] receptors[edit]

Antagonism of the 5-HT[SUB]2[/SUB] subfamily of receptors and inverse agonism of the 5-HT[SUB]2C[/SUB] receptor appears to be in part responsible for mirtazapine's efficacy in the treatment of depressive states.[SUP][78][/SUP][SUP][79][/SUP] Mirtazapine increases dopamine release in the prefrontal cortex.[SUP][80][/SUP][SUP][81][/SUP] Accordingly, it was shown that by blocking the α[SUB]2[/SUB]-adrenergic receptors and 5-HT[SUB]2C[/SUB] receptors mirtazapine disinhibited dopamine and norepinephrine activity in these areas in rats.[SUP][82][/SUP] In addition, mirtazapine's antagonism of 5-HT[SUB]2A[/SUB] receptors has beneficial effects on anxiety, sleep and appetite, as well as sexual function regarding the latter receptor.[SUP][7][/SUP][SUP][42][/SUP] Mirtazapine has been shown to lower drug seeking behaviour in various human and animal studies.[SUP][83][/SUP][SUP][84][/SUP][SUP][85][/SUP] It is also being investigated in substance abuse disorders to reduce withdrawal effects and improve remission rates.[SUP][83][/SUP][SUP][86][/SUP][SUP][87][/SUP][SUP][88][/SUP]
Antagonism of the 5-HT[SUB]3[/SUB] receptor, an action mirtazapine shares with the approved antiemetic ondansetron, significantly improves pre-existing symptoms of nausea, vomiting, diarrhea, and irritable bowel syndrome in afflicted individuals.[SUP][89][/SUP] Mirtazapine may be used as an inexpensive antiemetic alternative to ondansetron.[SUP][24][/SUP] Blockade of the 5-HT[SUB]3[/SUB] receptors has also shown to improve anxiety and to be effective in the treatment of drug addiction in several studies.[SUP][90][/SUP] In conjunction with substance abuse counseling, mirtazapine has been investigated for the purpose of reducing methamphetamine use in dependent individuals with success.[SUP][84][/SUP] In contrast to mirtazapine, the SSRIs, SNRIs, MAOIs, and some TCAs increase the general activity of the 5-HT[SUB]2A[/SUB], 5-HT[SUB]2C[/SUB], and 5-HT[SUB]3[/SUB] receptors leading to a host of negative changes and side effects, the most prominent of which including anorexia, insomnia, sexual dysfunction (loss of libido and anorgasmia), nausea, and diarrhea, among others. As a result, it is often combined with these drugs to reduce their side-effect profile and to produce a stronger antidepressant effect.[SUP][42][/SUP][SUP][91][/SUP]
Mirtazapine does not have serotonergic activity and does not cause serotonergic side effects or serotonin syndrome.[SUP][9][/SUP][SUP][92][/SUP] This is in accordance with the fact that it is not a serotonin reuptake inhibitor or MAOI, nor a serotonin receptor agonist.[SUP][9][/SUP][SUP][92][/SUP] There are no reports of serotonin syndrome in association with mirtazapine alone, and mirtazapine has not been found to cause serotonin syndrome in overdose.[SUP][9][/SUP][SUP][92][/SUP][SUP][93][/SUP] However, there are a handful of case reports of serotonin syndrome occurring with mirtazapine in combination with serotonergic drugs like SSRIs, although such reports are unusual, very rare, and do not necessarily implicate mirtazapine as causative.[SUP][9][/SUP][SUP][94][/SUP][SUP][95][/SUP][SUP][96][/SUP][SUP][97][/SUP][SUP][98][/SUP] The addition of mirtazapine to an MAOI does not cause serotonin syndrome, and has been considered to be a safe combination.[SUP][9][/SUP][SUP][92][/SUP] Moreover, mirtazapine may actually be useful in the treatment of serotonin syndrome, with at least one publication finding it to be effective in resolving the syndrome.[SUP][9][/SUP][SUP][99][/SUP][SUP][100][/SUP] This is in accordance with the fact that the 5-HT[SUB]2A[/SUB] receptor is the predominant serotonin receptor thought to be involved in the pathophysiology of serotonin syndrome (with the 5-HT[SUB]1A[/SUB] receptor seeming to be protective).[SUP][9][/SUP][SUP][92][/SUP] Mirtazapine is a potent 5-HT[SUB]2A[/SUB] receptor antagonist, and cyproheptadine, a drug that shares this property, mediates recovery from serotonin syndrome and is well-established clinically as an antidote against it.[SUP][9][/SUP][SUP][101][/SUP]
H[SUB]1[/SUB] receptor[edit]

Mirtazapine is a very strong H[SUB]1[/SUB] receptor inverse agonist and, as a result, it can cause powerful sedative and hypnotic effects.[SUP][7][/SUP] A single 15 mg dose of mirtazapine to healthy volunteers has been found to result in over 80% occupancy of the H[SUB]1[/SUB] receptor and to induce intense sleepiness.[SUP][72][/SUP] After a short period of chronic treatment, however, the H[SUB]1[/SUB] receptor tends to desensitize and the antihistamine effects become more tolerable. Many patients may also dose at night to avoid the effects, and this appears to be an effective strategy for combating them. Blockade of the H[SUB]1[/SUB] receptor may improve pre-existing allergies, pruritus, nausea, and insomnia in afflicted individuals. It may also contribute to weight gain, however. In contrast to the H[SUB]1[/SUB] receptor, mirtazapine has only low affinity for the muscarinic acetylcholine receptors, although anticholinergic side effects like dry mouth, constipation, and mydriasis are still sometimes seen in clinical practice.[SUP][102][/SUP]
Pharmacokinetics[edit]

The oral bioavailability of mirtazapine is about 50%. It is found mostly bound to plasma proteins, about 85%. It is metabolized primarily in the liver by demethylation and hydroxylation via cytochrome P450 enzymes. One of its major metabolites is desmethylmirtazapine. The overall elimination half-life is 20–40 hours. About 15% is eliminated in feces and 75% in urine.[SUP][103][/SUP][SUP]:430[/SUP]
History[edit]

Mirtazapine was first synthesized at Organon and published in 1989, was first approved for use in major depressive disorder in the Netherlands in 1994, and was introduced in the United States in 1996 under the brand name Remeron.[SUP][103][/SUP][SUP]:429[/SUP][SUP][104][/SUP][SUP][105][/SUP]
Society and culture[edit]


A 15 mg tablet of generic mirtazapine.​

Generic names[edit]

Mirtazapine is the English and French generic name of the drug and its INN, USAN, USP, BAN, DCF, and JAN.[SUP][1][/SUP][SUP][2][/SUP][SUP][106][/SUP] Its generic name in Spanish is mirtazapina, in German is Mirtazapin, and in Latin is mirtazapinum.[SUP][1][/SUP][SUP][2][/SUP]
Brand names[edit]

Mirtazapine is marketed under many brand names worldwide, including Adco-Mirteron, Afloyan, Amirel, Arintapin Smelt, Avanza, Azapin, Beron, Bilanz, Calixta, Ciblex, Combar, Comenter, Depreram, Divaril, Esprital, Maz, Menelat, Mepirzapine, Merdaten, Meronin, Mi Er Ning, Milivin, Minelza, Minivane, Mirastad, Mirazep, Miro, Miron, Mirrador, Mirt, Mirta, Mirtabene, Mirtadepi, Mirtagamma, Mirtagen, Mirtalan, Mirtamor, Mirtamylan, Mirtan, Mirtaneo, Mirtapax, Mirtapil, Mirtapine, Mirtaron, Mirtastad, Mirtax, Mirtaz, Mirtazap, Mirtazapin, Mirtazapina, Mirtazapine, Mirtazapinum, Mirtazelon, Mirtazon, Mirtazonal, Mirtel, Mirtimash, Mirtin, Mirtine, Mirzapine, Mirzaten, Mirzest, Mitaprex, Mitaxind, Mitocent, Mitrazin, Mizapin, Motofen, Mytra, Norset, Noxibel, Pharmataz, Promyrtil, Ramure, Redepra, Reflex, Remergil, Remergon, Remeron, Remirta, Rexer, Saxib, Sinmaron, Smilon, Tazepin, Tazimed, Tetrazic, Tifona, U-Mirtaron, U-zepine, Valdren, Vastat, Velorin, Yarocen, Zania, Zapex, Zestat, Zismirt, Zispin, Zuleptan, and Zulin.[SUP][2][/SUP]
Chemistry[edit]

Mirtazapine is a tetracyclic piperazinoazepine; mianserin was developed by the same team of organic chemists and mirtazapine differs from it via addition of a nitrogen atom in one of the rings.[SUP][103][/SUP][SUP]:429[/SUP][SUP][107][/SUP][SUP][108][/SUP] It is a racemic mixture of enantiomers. The (S)-(+)-enantiomer is known as esmirtazapine.
Analogues of mirtazapine include mianserin, setiptiline, and aptazapine.
Synthesis[edit]

A chemical synthesis of mirtazapine has been published.[SUP][109][/SUP]
Research[edit]

The use of mirtazapine has been explored in several additional conditions:



Veterinary use[edit]

Mirtazapine is sometimes prescribed as an appetite stimulant for cats or dogs experiencing anorexia due to medical conditions such as chronic kidney disease. It is especially useful for treating combined poor appetite and nausea in cats and dogs.[SUP][123][/SUP][SUP][124][/SUP]
V comin outta left field to drop some knowledge on my bitch ass lol. That stuff is very intriguing. However, I'm nervous when it comes to brain chemicals. Anti-D's have been something that I hear too many horror stories about.
 

Pushtoday

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When should you use GHRP 6?

GHRP 6 is most commonly used for growth hormone replacement therapy. It is normally chosen by users because of the obvious cost advantage it offers.
Growth hormones are restricted by stringent laws hence, more and more people are turning in to GHRP 6 use. GHRP 6 is used to enhance skin and improve increase muscle gain and fat loss.

It is also used in conjunction with other anabolic steroids to promote greater synergistic effects which includes increased recovery from injuries.

What makes GHRP 6 a unique and useful peptide is that, you longer need to cycle it to receive all the benefits it offers.
You may use it for prolonged periods of time for any of the abovementioned reasons.
However, you must ensure to limit the dosage to the minimum suggested dosage range when you intent to use it on an ongoing basis.


Ok brothers, This is one of the peptides on the top of my wish list.
I'm thinking on a cruise would be a good time to give this a shot.
Seems like a lot of benefits for the cost?
 
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