D2 and 5-HT2 antagonist with antipsychotic (neuroleptic) and antiemetic efficacy.
Perospirone (SM-9018) is a typical neuroleptic (antipsychotic) agent that displays high affinity for 5-HT2, D2 and 5-HT1A receptors (Ki = 0.61, 1.4 and 2.9-1.8 nM, respectively), moderate affinity for alpha 1 and D1 receptors (Ki = 17 and 41 nM, respectively), while exhibiting much reduced affinity for alpha 2 (Ki = 408 nM) and little affinity toward muscarinic, opiate, glutamate, phencyclidine, benzodiazepine or GABAA receptors (Ki >1 μM). SM-9018 antagonizes both D2-dependent (e.g. methamphetamine-induced hyperactivity, apomorphine-induced stereotypy) and 5-HT2-mediated (e.g. tryptamine-induced clonic seizure) activities in vivo, while exhibiting very low cataleptogenic and central depressant activities commonly observed with two other neuroleptics, haloperidol and chlorpromazine.
1. Changes in behavioral dopaminergic and serotonergic sensitivities were studied in rats after withdrawal of the chronic treatments with SM-9018 (0.1 mg/kg/day), a potential atypical neuroleptic, and with haloperidol (0.3 mg/kg/day) using continuous infusion pumps. 2. Administration of SM-9018 inhibited
Japanese journal of pharmacology, 53(3), 321-329 (1990-07-01)
Pharmacological studies were undertaken to clarify the profile of cis-2-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl) butyl) hexahydro-1H-isoindole-1,3-(2H)-dione hydrochloride (SM-9018), a new neuroleptic drug. SM-9018 had very high binding affinities for both 5-hydroxytryptamine2 (5-HT2) and dopamine2 (D2) receptors, unlike many other neuroleptics. SM-9018 also strongly inhibited
Drug metabolism and pharmacokinetics, 31(6), 395-404 (2016-10-18)
The effect of drugs in the central nervous system (CNS) is closely related to occupancy of their target receptor. In this study, we integrated plasma concentrations, in vitro/in vivo data for receptor or protein binding, and in silico data, using a physiologically
Pharmacology, biochemistry, and behavior, 49(1), 19-23 (1994-09-01)
Induction of bradykinesia by SM-9018, a novel 5-HT2 and D2 antagonist, was compared with that of other neuroleptics using the pole test in mice. Neuroleptics including SM-9018, haloperidol, chlorpromazine, and thioridazine dose dependently induced bradykinesia in the pole-descending behavior of
Progress in neuro-psychopharmacology & biological psychiatry, 19(6), 1091-1101 (1995-10-01)
1. Receptor binding and behavioral studies were performed to compare the effects of subchronic treatments with SM-9018, a novel 5-HT2 and D2 antagonist, and with haloperidol (HAL) on dopamine and 5-HT receptors in rats. 2. SM-9018 treatment (10 mg/kg/day p.o.)
Our team of scientists has experience in all areas of research including Life Science, Material Science, Chemical Synthesis, Chromatography, Analytical and many others.
