![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 7 of 7. This is the beginning of the thread.
Posted by mike1975 on November 24, 2008, at 19:27:58
Hi guys,
What do you think of this new anti-psychotic?
Take care
Mike
Posted by jrbecker76 on November 24, 2008, at 22:20:06
In reply to Asenapine - new hope or all the same, posted by mike1975 on November 24, 2008, at 19:27:58
> Hi guys,
>
> What do you think of this new anti-psychotic?
>
> http://www.marketwatch.com/news/story/Schering-Plough-Unveils-Top-Line/story.aspx?guid=%7B2B848E13-A93F-49A7-A221-BC61F162DD46%7D
>
> Take care
>
> MikeMike-
Louis,
It looks like the FDA will have to finish its big hiring initiative before they'll be able to stick to getting anything approved according to their original PDUFA timelines. Hopefully, the agency will give a ruling on Saphris (Asenapine)in the next couple of months.
Asenapine, at least on paper, looks like a pretty interesting profile....many have hyped it as the next AP blockbuster. It will probably be a little activating like Ziprasidone, and leave very little incidence of hyperprolatictinemia and weight gain. By its high affinity for 5-HT2C, it will be a good candidate to impact negative symptoms. It's weakness as a stand-alone AP though might be that it's not that sedating (i.e., won't fulfill a role like Seroquel does to address sleep as well as other symptoms...although this profile might be in fact a positive attribute for many); and secondly, it needs twice daily dosing. Also, the drug's original co-developer, Pfizer, dropped out after Ph III studies were complete. You have to wonder why. But still, it looks to be pretty interesting.
Click here for a topline PPT review:
akzonobel-ccna.com/misc/downloadabledoc.asp?tp=0&id=vWmL7JQ22j0%3D&number=1&l=English
JB
Posted by desolationrower on November 25, 2008, at 1:55:56
In reply to Re: SaphrisTM(Asenapine)- new hope or all the same » mike1975, posted by jrbecker76 on November 24, 2008, at 22:20:06
Differential regional and dose-related effects of asenapine on dopamine receptor subtypes
JournalPsychopharmacology
Abstract
Rationale The novel psychopharmacologic agent, asenapine, has high affinity for a range of receptors including the dopaminergic receptors.
Objective We examined the long-term effects of multiple doses of asenapine on dopamine receptor subtypes: D1-like (D1 and D5), D2, D3, and D4.
Methods Rats were given asenapine 0.03, 0.1, or 0.3 mg/kg (subcutaneously, twice daily) or vehicle for 4 weeks. Receptor binding was determined by autoradiography from brain sections collected from the medial prefrontal cortex (mPFC), dorsolateral frontal cortex, caudate putamen (CPu), nucleus accumbens (NAc), and hippocampus (HIP).
Results Four weeks of asenapine at 0.3 mg/kg significantly (P < 0.05) increased D1-like binding in the mPFC (by 26%), NAc (59%), and CPu (55%). Asenapine (0.1 and 0.3 mg/kg) also increased D2 binding in mPFC (43% and 55%, respectively). All doses of asenapine dose-dependently increased D2 binding in HIP (by 32%, 45%, and 63%, respectively). In contrast, only 0.3 mg/kg of asenapine significantly (P < 0.05) increased D2 binding in the NAc (32%) and CPu (41%). Repeated treatment with 0.1 and 0.3 mg/kg of asenapine increased D4 binding in the NAc (36% and 71%), CPu (27% and 70%), and HIP (48% and 77%). However, asenapine, at the doses tested, did not significantly alter D3 binding in the brain regions examined in this study.
Conclusions These results indicate that asenapine has region-specific and dose-dependent effects on dopamine receptor subtypes in rat forebrain, which may contribute to asenapines unique psychopharmacological properties.Asenapine, a novel psychopharmacologic agent: preclinical evidence for clinical effects in schizophrenia
JournalPsychopharmacology
Abstract
Rationale Asenapine is a novel psychopharmacologic agent being developed for the treatment of schizophrenia and bipolar disorder.
Materials and methods The present study was undertaken to investigate the effects of asenapine using animal models predictive of antipsychotic efficacy (conditioned avoidance response [CAR]) and extrapyramidal side effects (EPS; catalepsy). In parallel, the effects of asenapine on regional dopamine output using in vivo microdialysis in freely moving rats, dopamine output in the core and shell subregions of nucleus accumbens (NAc) using in vivo voltammetry in anesthetized rats, and N-methyl-d-aspartate (NMDA)-induced currents in pyramidal neurons of the medial prefrontal cortex (mPFC) using the electrophysiological technique intracellular recording in vitro were assessed.
Results Asenapine (0.050.2 mg/kg, subcutaneous [s.c.]) induced a dose-dependent suppression of CAR (no escape failures recorded) and did not induce catalepsy. Asenapine (0.050.2 mg/kg, s.c.) increased dopamine efflux in both the mPFC and the NAc. Low-dose asenapine (0.01 mg/kg, intravenous [i.v.]) increased dopamine efflux preferentially in the shell compared to the core of NAc, whereas at a higher dose (0.05 mg/kg, i.v.), the difference disappeared. Finally, like clozapine (100 nM), but at a considerably lower concentration (5 nM), asenapine significantly potentiated the NMDA-induced responses in pyramidal cells of the mPFC.
Conclusions These preclinical data suggest that asenapine may exhibit highly potent antipsychotic activity with very low EPS liability. Its ability to increase both dopaminergic and glutamatergic activity in rat mPFC suggests that asenapine may possess an advantageous effect not only on positive symptoms in patients with schizophrenia, but also on negative and cognitive symptomsAbstract Asenapine, a novel psychopharmacologic agent being developed for the treatment of schizophrenia and bipolar disorder, has high affinity for a wide range of receptors, including the serotonergic receptors 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5A, 5-HT6 and 5-HT7. We examined the long-term effects in rat brain of multiple doses of asenapine on representative serotonin receptor subtypes: 5-HT1A, 5-HT2A and 5-HT2C. Rats were given asenapine (0.03, 0.1 or 0.3 mg/kg) subcutaneously twice daily or vehicle for 4 weeks. Brain sections were collected from the medial prefrontal cortex (mPFC), dorsolateral frontal cortex (DFC), caudate putamen, nucleus accumbens, hippocampal CA1 and CA3 regions, and entorhinal cortex and processed for in-vitro receptor autoradiography. Asenapine 0.1 and 0.3 mg/kg significantly increased 5-HT1A binding in mPFC (by 24% and 33%, respectively), DFC (27%, 31%) and hippocampal CA1 region (23%, 25%) (all P < 0.05). All three asenapine doses (0.03, 0.1 and 0.3 mg/kg) significantly decreased 5-HT2A binding by a similar degree in mPFC (40%, 44%, 47%, respectively) and DFC (45%, 51%, 52%) (all P < 0.05), but did not alter 5-HT2A binding in the other brain regions studied. In contrast to the effects on 5-HT1A and 5-HT2A receptors, asenapine did not alter 5-HT2C binding in any brain region examined at the doses tested. Our results indicate that repeated administration of asenapine produces regional-specific effects on 5-HT1A and 5-HT2A receptors in rat forebrain regions, which may contribute to the distinctive psychopharmacologic profile of asenapine.
The location-specific binding is quite interesting. Couldnt' find anything on how tightly it binds which i think it key to atpyicality. I think that it will at minimum be a different feeling drug from anything we currently have. I'm interested, especially as it appears to not have significant nasty side effects (at least, compared to other APs). THere was one study showing it less effective than olanzapine i think, wonder if it was a dosing issue.-d/r
Posted by B2chica on November 25, 2008, at 11:57:41
In reply to Re: SaphrisTM(Asenapine)- new hope or all the same, posted by desolationrower on November 25, 2008, at 1:55:56
i'm glad you mentioned the comparison study to olanzapine, i immediately thought of this as it is to effect D1 and none of the other AP's effect that right now.
i'm very anxious to see this out and to see real results.
i'd be willing to give it a go.b2c.
>
> The location-specific binding is quite interesting. Couldnt' find anything on how tightly it binds which i think it key to atpyicality. I think that it will at minimum be a different feeling drug from anything we currently have. I'm interested, especially as it appears to not have significant nasty side effects (at least, compared to other APs). THere was one study showing it less effective than olanzapine i think, wonder if it was a dosing issue.
>
> -d/r
Posted by mike1975 on November 26, 2008, at 9:45:52
In reply to Re: SaphrisTM(Asenapine)- new hope or all the same » desolationrower, posted by B2chica on November 25, 2008, at 11:57:41
Guys,
Thank you very much for all your replies. There is another AP in development. However, it is years away from market:
It says it is 5-ht6 antagonist. It does not tell me anything. If you do not mind please explain.
Thank you
Mike
Posted by Jeroen on November 26, 2008, at 11:28:42
In reply to Re: SaphrisTM(Asenapine)- new hope or all the same » mike1975, posted by jrbecker76 on November 24, 2008, at 22:20:06
sorry but my experimental pdoc sais its pretty sedating
Posted by jrbecker76 on January 14, 2009, at 9:42:20
In reply to Re: SaphrisTM(Asenapine)- new hope or all the same, posted by Jeroen on November 26, 2008, at 11:28:42
although the FDA is requesting more data, it looks to be closer to approval.....
http://money.cnn.com/news/newsfeeds/articles/djf500/200901140712DOWJONESDJONLINE000501_FORTUNE5.htm
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.