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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by SLS on March 11, 2010, at 13:08:59
Iloperidone (Fanapt) acts as an antagonist at many of the usual receptors that neuroleptics are known to occupy. However, it also binds potently to NE alpha-2a/c receptors as an antagonist - a property that it shares with mirtazapine (Remeron). Perhaps iloperidone will demonstrate antidepressant properties. Iloperidone also blocks 5-HT7 receptors with moderate affinity. 5-HT7 antagonists are being looked at for the treatment of depression. It may be important, however, to note that iloperidone blocks 5-HT1a receptors. This is in contrast to aripiprazole, ziprasidone, gepirone and vilazodone - all of which are 5-HT1a agonists that display antidepressant activity.
One advantage to iloperidone is that it does not block histamine H1 receptors. This might avoid the occurrences of weight gain and diabetes. If this is true, iloperidone would be only the second atypical antipsychotic that is weight-neutral; the other drug being ziprasidone. Iloperidone does block 5-HT2c receptors, though. It will be interesting to see if weight neutrality by iloperidone is demonstrated despite this effect.
- Scott
Posted by Brainbeard on March 11, 2010, at 14:16:47
In reply to - Interesting Antipsychotic, posted by SLS on March 11, 2010, at 13:08:59
Ziprasidone's weight neutrality is actually rather surprising if you look at its pharmacological profile (http://www.nature.com/npp/journal/v28/n3/fig_tab/1300027t1.html) - medium strong 5HT2C-antagonist, also touches H1..
Posted by SLS on March 12, 2010, at 10:52:41
In reply to Re: - Interesting Antipsychotic, posted by Brainbeard on March 11, 2010, at 14:16:47
> Ziprasidone's weight neutrality is actually rather surprising if you look at its pharmacological profile (http://www.nature.com/npp/journal/v28/n3/fig_tab/1300027t1.html) - medium strong 5HT2C-antagonist, also touches H1..
Nice chart.Thanks.
- Scott
Posted by desolationrower on March 31, 2010, at 21:14:22
In reply to Re: - Interesting Antipsychotic » Brainbeard, posted by SLS on March 12, 2010, at 10:52:41
i think most atypicals antagonise andrenoceptors to some extent
-d/r
Posted by SLS on April 1, 2010, at 19:02:07
In reply to Re: - Interesting Antipsychotic, posted by desolationrower on March 31, 2010, at 21:14:22
> i think most atypicals antagonise andrenoceptors to some extent
>
> -d/r
Life Sci. 2000 Nov 24;68(1):29-39.
Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds.Richelson E, Souder T.
Department of Psychiatry and Psychology, and Pharmacology, Mayo Foundation for Medical Education and Research and Mayo Clinic, Jacksonville, FL 32224, USA. [email protected]
Using radioligand binding assays and post-mortem normal human brain tissue, we obtained equilibrium dissociation constants (K(d)s) for nine new antipsychotic drugs (iloperidone, melperone, olanzapine, ORG 5222, quetiapine, risperidone, sertindole, ziprasidone, and zotepine), one metabolite of a new drug (9-OH-risperidone), and three older antipsychotics (clozapine, haloperidol, and pimozide) at nine different receptors (alpha1-adrenergic, alpha2-adrenergic, dopamine D2, histamine H1, muscarinic, and serotonin 5-HT1A, 5-HT1D, 5-HT2A, and 5-HT2C receptors). Iloperidone was the most potent drug at the two adrenergic receptors. ORG 5222 was the most potent drug at dopamine D2 and 5-HT2c receptors, while ziprasidone was the most potent compound at three serotonergic receptors (5-HT1A, 5-HT1D, and 5-HT2A). At the remaining two receptors, olanzapine was the most potent drug at the histamine H1 receptor (Kd=0.087 nM); clozapine at the muscarinic receptor (Kd=9 nM). Certain therapeutic and adverse effects, as well as certain drug interactions can be predicted from a drug's potency for blocking a specific receptor. These data can provide guidelines for the clinician in the choice of antipsychotic drug.
Posted by SLS on April 2, 2010, at 7:15:48
In reply to Re: - Interesting Antipsychotic, posted by SLS on April 1, 2010, at 19:02:07
Here's the one that I couldn't find the other day.
- Scott
----------------------------------------------------
Eur J Pharmacol. 2003 Feb 21;462(1-3):33-40.
alpha2C-Adrenoceptor blockade by clozapine and other antipsychotic drugs.Kalkman HO, Loetscher E.
Novartis Pharma AG, Research Nervous System, Building WSJ-360-405, CH-4002 Basel, Switzerland. [email protected]
The noradrenergic system may play a role in antipsychotic modulation of schizophrenia symptoms. Therefore, the antagonistic potencies of the antipsychotics clozapine, chlorpromazine, risperidone, olanzapine, haloperidol, quetiapine, ziprasidone, iloperidone and aripiprazole were quantified using cell lines expressing the recombinant human alpha(2C)-adrenoceptor, alpha(2A)-adrenoceptor, or dopamine D(2L) receptor. The alpha(2)-adrenoceptor antagonists, yohimbine and idazoxan, were also tested. Alterations in cAMP were measured as changes in luminescence. In the alpha(2A)-adrenoceptor cell line, the agonist 5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline (UK14,304) induced a concentration-dependent increase in luminescence. In cell lines expressing alpha(2C) and D(2L) receptors, agonists induced a concentration-dependent reduction in luminescence. Yohimbine and idazoxan were the most potent alpha(2A)-adrenoceptor antagonists, yohimbine and iloperidone were the most potent alpha(2C)-adrenoceptor antagonists, and haloperidol and olanzapine were the most potent dopamine D(2) receptor antagonists. Clozapine had the highest alpha(2C)/D(2) selectivity, and iloperidone the highest alpha(2C)/alpha(2A) ratio. It is hypothesised that alpha(2C)-adrenoceptor blockade contributes to improvement of cognitive function.
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