![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by lunesta on December 12, 2005, at 7:12:12
Apparently both of these drugs have nearly the exact same binding profile for the melatonergic system at the MT1 and MT2 receptors as agonists.
What is interesting is that Valdoxan is being studied and almost done with trials in Europe for depression with very unique and good results, with nearly no side effects, while at the same time, the drug Rozerem, just approved and out in the USA is being used for insomnia rather than depression.
They both work on the same exact receptors, with nearly the same affinity.
So here is the cool thing, there is studies on pubmed.com suggesting that Rozerem shows antidepressant action as well.
The key difference though may be the dosing, , as well as the "nearly" identical, but not 100% identical binding sites, some of which may not yet be identified for Valdoxan, making it more antidepressant like, than Rozerem.
What I am suggesting is that Rozerem may have significant antidepressant properties equivalent to Valdoxan (not out yet) and that it may be worth trying off label or in higher dosages for depression and/or sleep disorder.
Usually sleep/depression/cycidian rythm disturbance is messed up in depression, so you may see how both drugs could actually help sleep and depression.
Rozerem is currently available, as a non controlled substance for insomnia in the USA.
I would like to hear of anyones experience with it for, insomnia, sleep onset, or depression relief as a side effect.
Thanks
lunesta
Posted by tygereyes on December 12, 2005, at 8:46:29
In reply to Valdoxan vs Rozerem - nearly identical - ADsleep, posted by lunesta on December 12, 2005, at 7:12:12
Rozerem worked beautifully for insomnia - for a few days. Then, like many insomnia drugs, it stopped working completely. In two week's time I was taking triple the dosage and still having to take Seroquel or Lunesta or both. Good luck - hope your experience with it is different.
Posted by jrbecker on December 12, 2005, at 10:18:41
In reply to Valdoxan vs Rozerem - nearly identical - ADsleep, posted by lunesta on December 12, 2005, at 7:12:12
> Apparently both of these drugs have nearly the exact same binding profile for the melatonergic system at the MT1 and MT2 receptors as agonists.
>
> What is interesting is that Valdoxan is being studied and almost done with trials in Europe for depression with very unique and good results, with nearly no side effects, while at the same time, the drug Rozerem, just approved and out in the USA is being used for insomnia rather than depression.
>
> They both work on the same exact receptors, with nearly the same affinity.
>
> So here is the cool thing, there is studies on pubmed.com suggesting that Rozerem shows antidepressant action as well.
>
> The key difference though may be the dosing, , as well as the "nearly" identical, but not 100% identical binding sites, some of which may not yet be identified for Valdoxan, making it more antidepressant like, than Rozerem.
>
> What I am suggesting is that Rozerem may have significant antidepressant properties equivalent to Valdoxan (not out yet) and that it may be worth trying off label or in higher dosages for depression and/or sleep disorder.
>
> Usually sleep/depression/cycidian rythm disturbance is messed up in depression, so you may see how both drugs could actually help sleep and depression.
>
> Rozerem is currently available, as a non controlled substance for insomnia in the USA.
>
> I would like to hear of anyones experience with it for, insomnia, sleep onset, or depression relief as a side effect.
>
> Thanks
> lunestaas scott mentioned above, rozerem (ramelteon) is not identical in its pharmacological actions to valdoxan (agomelatine). although they are both melatonergic agonists with a short-half life, the key difference is that agomelatine is also a potent 5-HT2C antagonist. Studies have revealed that its >primary< antidepressant mechanism is via this receptor's inactivation....
Psychopharmacology (2005) 177: 1–12
Mark J. Millan . Mauricette Brocco . Alain Gobert .Anne Dekeyne
Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade
Abstract Rationale: The novel antidepressant agent, agomelatine, behaves as an agonist at melatonin receptors and as an antagonist at serotonin (5-HT)2C receptors. Objectives: To determine whether, by virtue of its antagonist
properties at 5-HT2C receptors, agomelatine elicits anxiolytic properties in rats. Methods: Employing a combined neurochemical and behavioural approach, actions of agomelatine were compared to those of melatonin, the selective 5-HT2C receptor antagonist, SB243,213, and the benzodiazepine, clorazepate. Results: In unfamiliar pairs of rats exposed to a novel
environment, agomelatine enhanced the time devoted to active social interaction, an action mimicked by clorazepate and by SB243,213. In a Vogel conflict procedure, agomelatine likewise displayed dose-dependent anxiolytic activity with a maximal effect comparable to clorazepate,
and SB243,213 was similarly active in this procedure. In a plus-maze procedure in which clorazepate significantly enhanced percentage entries into open arms, agomelatine revealed only modest activity and SB243,213 was inactive. Further, like SB243,213, and in contrast to clorazepate, agomelatine did not suppress ultrasonic vocalizations emitted by rats re-exposed to an environment associated with an aversive stimulus. Whereas clorazepate
reduced dialysate levels of 5-HT and noradrenaline in hippocampus and frontal cortex of freely moving rats, agomelatine did not affect extracellular levels of 5-HT and
elevated those of noradrenaline. SB243,213 acted similarly to agomelatine. Melatonin, which did not modify extracellular levels of 5-HT or noradrenaline, was ineffective in all models of anxiolytic activity. Furthermore,
the selective melatonin antagonist, S22153, did not modify anxiolytic properties of agomelatine in either the social interaction or the Vogel Conflict tests. Conclusions: In contrast to melatonin, and reflecting blockade of 5-HT2C receptors, agomelatine is active in several models of anxiolytic properties in rodents. The
anxiolytic profile of agomelatine differs from that of benzodiazepines from which it may also be distinguished by its contrasting influence on corticolimbic monoaminergic pathways.
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 306, No. 3M. J. MILLAN, A. GOBERT, F. LEJEUNE, A. DEKEYNE, A. NEWMAN-TANCREDI, V. PASTEAU, J.-M. RIVET, and
D. CUSSACThe Novel Melatonin Agonist Agomelatine (S20098) Is an Antagonist at 5-Hydroxytryptamine2C Receptors, Blockade of Which Enhances the Activity of Frontocortical Dopaminergic
and Adrenergic PathwaysABSTRACT
Agomelatine (S20098) displayed pKi values of 6.4 and 6.2 at native(porcine) and cloned, human (h)5-hydroxytryptamine (5-HT)2C receptors,
respectively. It also interacted with h5-HT2B receptors(6.6), whereas it showed low affinity at native (rat)/cloned, human 5-HT2A (_5.0/5.3) and 5-HT1A (_5.0/5.2) receptors, and negligible
(_5.0) affinity for other 5-HT receptors. In antibody capture/scintillation proximity assays, agomelatine concentration dependently
and competitively abolished h5-HT2C receptor-mediated activation of Gq/11 and Gi3 (pA2 values of 6.0 and 6.1). As measured by [3H]phosphatidylinositol depletion, agomelatine abolished activation of phospholipase C by h5-HT2C (pKB value of 6.1)and h5-HT2B (pKB value of 6.6) receptors. In vivo, it dose dependently
blocked induction of penile erections by the 5-HT2C agonists (S)-2-(6-chloro-5-fluoroindol-1-yl)-1-methylethylamine (Ro60,0175) and 1-methyl-2-(5,8,8-trimethyl-8H-3-aza-cyclopenta[
a]inden-3-yl) ethylamine (Ro60,0332). Furthermore, agomelatine dose dependently enhanced dialysis levels of dopamine in
frontal cortex of freely moving rats, whereas they were unaffected in nucleus accumbens and striatum. Although the electrical activity
of ventrotegmental dopaminergic neurons was unaffected by agomelatine, it abolished their inhibition by Ro60,0175. Extracellular
levels of noradrenaline in frontal cortex were also dose dependently enhanced by agomelatine in parallel with an acceleration in the firing rate of adrenergic cell bodies in the locus
coeruleus. These increases in noradrenaline and dopamine levels were unaffected by the selective melatonin antagonist N-[2-(5-
ethyl-benzo[b]thien-3-yl)ethyl] acetamide (S22153) and likely reflect blockade of 5-HT2C receptors inhibitory to frontocortical dopaminergic and adrenergic pathways. Correspondingly, in distinction to agomelatine, melatonin showed negligible activity at
5-HT2C receptors and failed to modify the activity of adrenergic and dopaminergic pathways. In conclusion, in contrast to melatonin, agomelatine behaves as an antagonist at 5-HT2B and 5-HT2C receptors: blockade of the latter reinforces frontocortical adrenergic and dopaminergic transmission.
Posted by lunesta on December 12, 2005, at 10:41:19
In reply to Re: Valdoxan vs Rozerem - not identical » lunesta, posted by jrbecker on December 12, 2005, at 10:18:41
5-HT2C receptor antagonists are Zofran (anti nesea chemo drug, and Remeron). I had a prescription for Zofran and it showed no effect , its a direct blocker of the 5ht2C, as well as remeron.
They to differ, but like i said, they are nearly identical. Maybe combining Zofran or Remeron with Rozerom would equal Valdoxans AD effects...
Posted by lunesta on December 12, 2005, at 10:46:04
In reply to Re: Valdoxan vs Rozerem - not identical » jrbecker, posted by lunesta on December 12, 2005, at 10:41:19
actually that would exactly mimik valdoxin. Take Rozerem, and Zofran, and there you go. Zofran is a direct blockade antagonist at 5ht2c receptors.
That could be interesting pharmacology.
Posted by jrbecker on December 12, 2005, at 11:47:36
In reply to Re: Valdoxan vs Rozerem - not identical » jrbecker, posted by lunesta on December 12, 2005, at 10:41:19
>
> They to differ, but like i said, they are nearly identical. Maybe combining Zofran or Remeron with Rozerom would equal Valdoxans AD effects...
>
>
uhm, they can't be nearly identical if the key difference (as well as the primary antidepressant mechanism itself) is the distinctive feature between these two compounds. but even meds that are actually in the same class, of course, have quite disparate differences -- SSRI's are the easiest example to conjure up. just something you should keep in mind.
JB
Posted by lunesta on December 12, 2005, at 13:02:25
In reply to Re: Valdoxan vs Rozerem - not identical, posted by jrbecker on December 12, 2005, at 11:47:36
Yes but the information we currently know about them shows they have the same binding sites (cept for the ht3 receptor in rozerems case). What I am saying is since its available in the US, there could be a good possibilty it could act as an antidepressant very similar to the other Valdoxan, adding Zofran, a highly selective tightly binding ht3 antagonist would be an interesting idea.
I am not saying they are 100% identical, but SSRI's are not a good example to quote since we know lexapro is the most serotonin selective, while paxil has lots of werid binding sites and zoloft hits dopamine etc etc.
Right now our knowlodge says we have 2 drugs that more or less hit the same receptors with more or less affinity probably, and add the 5ht3 receptor antagonism and based on all current knowlodge, we have identical drugs until we know more.A good example of this is how Proscar used for BPH turned into Propecia for MPB when they noticed that people were growing hair back from Proscar! Something along those lines. Perhaps with a little tweaking or more usage Rozerem could be an available AD with some added pharmacology and dosage adjustments.
Just an interesting idea to put out there.
Posted by Phillipa on December 12, 2005, at 20:35:51
In reply to Re: Valdoxan vs Rozerem - not identical » jrbecker, posted by lunesta on December 12, 2005, at 13:02:25
Rozeram I will google it. Fondly, Phillipa
Posted by ed_uk on December 14, 2005, at 15:47:07
In reply to Re: Valdoxan vs Rozerem - not identical » jrbecker, posted by lunesta on December 12, 2005, at 13:02:25
Hi
Zofran is a 5HT3 antagonist, not a 5HT2C antagonist.
ed
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.