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Why are melatonin receptor agonists being developed as antidepressants?

While Im sure their is a more scientific answer then this, my short answer would be "because pharmaceutical companies try to turn every fucking molecule into an antidepressant".

Have you heard of Stablon (tianeptine). It's a unique antidepressant and its mode of action is a serotonin reuptake ENHANCER.
For over 2 decades now, pharmaceutical companies have pushed serotonin reuptake inhibitors on the world as the final word in antidepressants. They have preached that low serotonin levels are the cause of depression, and depression can be cured by raising these levels by slowing the reuptake of serotonin.

And now we have a drug that does the exact opposite thing by increasing the rate of serotonin reuptake...and yet it is meant to treat the exact same condition (depression). -DG
 
perhaps the long term mood boost caused by ssris is not due to the increased serotonin levels, but due to the resultant effects on 5ht receptor expression in various parts of the brain. perhaps tianeptine causes a different, but still efficacious effect on 5ht expression.

oh, and just to remain on topic with the OP, perhaps the cascade of effects caused by certain melatonin agonists causes a change in 5ht receptor expression as well.

this is just good for thought for those of you with far more knowledge than me however. set me straight if there's something fundamentally misguided about my musings, i am just an amateur and would appreciate any enlightenment on the subject.
 
increased quality of sleep (esp. REM sleep) is undoubtably good for depression, its also supposed to cause balding men to grow back hair (cant hurt either!) ive been interested in melatonin agonists for a while (i remember talking to my psychiatrist about them almost four years ago) and i would really like to get my hands on some agomelatine, ultimately the answer to your question is this: all people have their own neurochemical composition and the greater variety of available ADs the better, my dad can only find relief from imipramine of all things - one mans poison is another mans life saving pharmaceutical.
 
Credit goes to rocknroll:

 
Agomelatine seems promising, the reuptake inhibitors (especially SSRIs) simpy lost my trust after having tried a few and reading a lot of reports on side effects and discontinuation symptoms. They sound soo...how to say, 'unselective' in the end lol.

Un fortunately for this novel drug we will have to wait until 2012 at least :P

Though there are many others 5-HT2c antagonists out there even if not so selective.
About this, I've always been curious on ergolines as a potential antidepressant, and in my opinion they should be further invetigated.
 
/navarone/ said:
Agomelatine seems promising...Unfortunately for this novel drug we will have to wait until 2012 at least :P
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I wouldn't hold my breath. I've talked to people who've used it as indicated and they say it's not that great.

I WOULD hold my breath for almorexant, but this is OT.
 
seep said:
I wouldn't hold my breath. I've talked to people who've used it as indicated and they say it's not that great.

I WOULD hold my breath for almorexant, but this is OT.
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Agomelatine has an half life of only a few hours and its recommend to take before going asleep so this results in absolutely no 5HT2C antagonism during the day.

I know of someone that took it every few hours during the day and said it was very effective.
 
As I recall, it wasn't thought to offer significant benefits over available SSRIs.
 
bupropion said:
Why wasn't saredutant approved? Are Substance P antagonists considered to cause euphoria or something?
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Sanofi shelved it to better weather the reception recession. Industry DB:

Trade Name: N/A
Generic Name: Saredutant, SR 48968
Company Name: sanofi-aventis
Medical Condition/Indication: Depression--Trial halted; Anxiety Disorders--Trial halted

Description: Neurokinin A overstimulates muscle by activating the NK2 receptor. Saredutant blocks NK2 receptors and prevents them from being stimulated. By reducing the effect of neurokinin A on intestinal tissue, hypermotility of the bowel may be decreased with this medication.

Saredutant, in an oral formulation, is currently in phase IIb clinical trials for the treatment of depression and anxiety and for irritable bowel syndrome.

In February 2004 Sanofi reported positive results from a phase IIb trial of Saredutant for the treatment of major depressive disorder. This double-blind, randomized, placebo- and fluoxetine-controlled multicenter trial enrolled 120 subjects per treatment arm. The subjects received placebo for 1 week, then were treated for a further 6 weeks. Saredutant was similar at 100 mg to fluoxetine 20 mg in reducing Hamilton-depression and Hamilton-anxiety scores (> -14 and -12, respectively). In the saredutant arm 43.9% exhibited a sustained response compared to 37.5% in the fluoxetine arm. In addition, saredutant demonstrated an improved adverse event profile compared with fluoxetine for any class adverse events (33.6 and 38.3%, respectively, versus 27.3% for placebo.

In December of 2004 Sanofi initiated two phase III trials of saredutant for the treatment of depression. One trial planned to enroll 450 subjects in the US and the other planned to enroll 450 subjects in France. The trials were designed to compare the efficacy of 100 mg saredutant to placebo.

In April of 2005 Sanofi initiated two phase III trials of saredutant for the treatment of depression. These US based, placebo-controlled trials planned to enroll 450 subjects each. The subjects were to receive placebo or 100 mg saredutant succinate for 8 weeks. The primary endpoint was change in Hamilton Depression Rating Scale (HAM-D) score at day 56. Results presented in February 2007 showed significant efficacy for saredutant compared to placebo, with reduced loss of sexual function. Adverse events were similar to placebo and were significantly less than paroxetine.

In May of 2005 Sanofi initiated a phase III trial of saredutant for the treatment of depression. This US based trial planned to enroll adult and elderly subjects with depression who were to receive 100 mg/day saredutant for 52 weeks. The primary endpoint was long-term safety and tolerability.

In May of 2006 Sanofi initiated a phase III trial of saredutant for the treatment of depression. This US based, 24- to 52-week, placebo controlled study planned to enroll 800 subjects with major depressive disorder. The subjects were to receive saredutant 100 mg, qd. The primary endpoint was the prevention of relapse of depressive symptoms.

In October of 2006 Sanofi initiated two phase III trials of saredutant for the treatment of generalized anxiety disorder (GAD).
The first trial was a placebo-controlled, randomized, double-blind study and planned to enroll 405 subjects in the US and Australia. The subjects were to receive placebo or 30 or 100 mg qd saredutant. The primary endpoint was change from baseline in HAM-A total score at day 56. Secondary endpoints included change from baseline at day 56 in a quality-of-life score.

The second trial was a placebo-controlled, randomized, double-blind study and planned to enroll 360 subjects in the US and Canada. The subjects were to receive placebo or 100 mg qd saredutant. The primary endpoint was change from baseline in HAM-A total score at day 56. Secondary endpoints included change from baseline at day 56 in a quality-of-life score.

In December of 2006 Sanofi initiated a phase III trial of saredutant for the treatment of depression. This placebo-controlled, randomized, double-blind study planned to enroll 375 elderly subjects with major depressive disorder in the US, Mexico, Russia, Turkey and Europe. The subjects were to receive placebo or 100 mg qd of saredutant. The primary endpoint was change from baseline in HAM-D total score at day 56 and secondary endpoints included change from baseline at day 56 in MADRS score and quality of life.

Also in December of 2006 Sanofi initiated a phase III trial for the treatment of GAD. This placebo-controlled, randomized, double-blind study planned to enroll 360 subjects in Europe, Canada and Turkey. The subjects were to receive placebo or 100 mg/day saredutant for 8 weeks. The primary endpoint was the change in Ham-A scale.

In January of 2007 Sanofi initiated a phase III trial of saredutant for the treatment of depression. This placebo-controlled, randomized, double-blind study planned to enroll 110 subjects with depression in the US. The subjects were to receive placebo 100 mg/day saredutant for 8 weeks. The pimary endpoint was change in daily number of discontinuation symptoms observed in the week after stopping treatment. Secondary endpoints included the proportion of subjects experiencing discontinuation symptoms.

As of February 2007 Sanofi was planning to initiate two phase III trials of saredutant for the treatment of generalized anxiety disorder (GAD) before the end of 2007. The first trial (EFC6757) planned to enroll 300 subjects and was to assess acute efficacy in the elderly. The second trial (EFC5586) was to recruit 340 subjects and was to assess long-term efficacy.

In April of 2009 Sanofi Aventis stopped the development of saredutant in an effort to contain cash resources.
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I always have a hard time with that forced swim test. I understand stand the reasoning, but I am not sure how well it translated....

The tail flick makes more sense to me, as with other nociceptive assaying devices...

This one is pretty strange

372150pic.jpg

It puts pressure on the paw until it flinches....
 
I remember foolishly taking 12mg of melatonin to try to abort a 14 gram mushroom trip and was unpleasantly surprised as it intensified the already horrible experience....

My worry with so-called "melatonergics" is the potential to increase prolactin levels and decrease testosterone levels. This is a big negative....
 
Yep. It's not a research chemical, it's a pharmaceutical.

I've ended up really liking ramelteon. It helps me sleep, produces amazing dreams, and it seems to regulate my mood some.
 
If you're interested in Agomelatine

Guys,

If you're interested in Agomelatine, there's a ~500 members forum (in english) called 'Agomelatine Psychonauts' @
http://groups.google.ca/group/agomelatine-psychonauts?hl=en

There's over a year of posts about experiences with it. They succeeded in making Agomelatine available for cheap at a time while it was only available in Ukraine (since a couple years there, btw). Note that I don't condone it, I'm just reporting it.

(If you apply, when ask why you're interested in the group, just answer 'Marty on Bluelight' and it will do the trick.)

I'll want to contribute to this thread (my personal experience, what can be concluded after about ~15 of following people trialling it, my hypothesis about its mechanism of action etc) in the next 48 hours. Just had the time to let you know about the group meanwhile.

Cheers
\/\/ /\/\
 
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