Effects of remoxipride and some related new substituted salicylamides on rat brain receptors.
A number of potential neuroleptic drugs of the substituted benzamide type have been compared with some reference neuroleptic drugs regarding their affinities for rat brain receptors using in vitro receptor binding techniques. The effects on dopamine-stimulated adenylate cyclase were also investigated. All 6-methoxysalicylamides were very potent inhibitors of the dopamine-D2 receptor and possessed much less affinity for other receptors as well as for the dopamine-stimulated adenylate cyclase. In contrast, the classical neuroleptic drugs were not selective dopamine-D2 receptor blockers. Several of these neuroleptics were thus potent inhibitors of alpha 1-receptors, 5-HT2 receptors, muscarinic receptors and histamine-H1 receptors. Sulpiride was the most selective dopamine-D2 receptor blocker of the reference compounds with a selectivity ratio of 65. The 6-methoxysalicylamides had selectivity ratios ranging from 18 to 167.
Hall
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Sällemark
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Jerning
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D000262:Adenylyl Cyclases / Q000032:analysis; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000031:analogs & derivatives / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D004294:Domperidone / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D017448:Receptors, Dopamine D2; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects; D017330:Remoxipride; D012457:Salicylamides / Q000494:pharmacology*; D013134:Spiperone / Q000378:metabolism; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000378:metabolism; D014316:Tritium
D014150:Antipsychotic Agents; D001549:Benzamides; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; D012457:Salicylamides; D013764:Tetrahydronaphthalenes; D017330:Remoxipride; D014316:Tritium; D013134:Spiperone; C011639:ADTN; D004294:Domperidone; C009074:N-n-propylnorapomorphine; D000262:Adenylyl Cyclases; D001058:Apomorphine; D004298:Dopamine