R-96544, also known as MPM, is a serotonin 5-HT2A receptor antagonist which is used in scientific research. It is also the active form of the laurate (dodecanoate) ester prodrug R-102444, which was investigated for potential medical use but was never marketed.
R-96544 shows high affinity for the serotonin 5-HT2A receptor (Ki = 1.6nM) and is selective for this receptor over various other targets. However, one exception is that it shows only 4-fold lower affinity for the serotonin 5-HT2C receptor relative to the serotonin 5-HT2A receptor. The drug inhibits serotonin-induced platelet aggregation in preclinical research and hence has antiplatelet effects. It also inhibits the pressor effects of serotonin in rodents. R-96544 is effective as a treatment in animal models of peripheral vascular disease and pancreatitis. It can attenuate the bradycardia induced by activation of the Bezold–Jarisch reflex by the serotonin 5-HT3 receptor agonist phenylbiguanide in rodents.
R-96544, similarly to other serotonin 5-HT2A receptor antagonists like ketanserin and ritanserin, blocks the hyperthermia induced by MDMA in rodents. It inhibits ethanol self-administration in rodents. On the other hand, the drug does not affect intracranial self-stimulation (ICSS) in rodents, though it can reverse the suppression of ICSS induced by the serotonin 5-HT2A receptor agonist TCB-2 and by the serotonin 5-HT2C receptor agonist WAY-161503. R-96544 has been found to facilitate long-term potentiation (LTP) in the anterior cingulate cortex (ACC) ex vivo. Application of R-96544 directly to certain brain areas has been found to inhibit fear- and seizure-induced analgesia in rodents. It inhibits the weight loss induced by the GLP-1 receptor agonist exendin-4 (EX4) in rodents, which appeared to be due specifically due to serotonin 5-HT2A receptor antagonism rather than due to actions at the serotonin 5-HT2C receptor.
The chemical synthesis of R-96544 has been described. A radiolabeled form of R-96544, known as [11C]MPM, has been studied as a positron emission tomography (PET) imaging tracer.
R-96544 was first described in the scientific literature by Naoki Tanaka and colleagues by 2000.
See also Serotonin 5-HT2A receptor antagonist R-102444 Sarpogrelate
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