title: 3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents.
abstract: A series of substituted phenethyl derivatives of 3-benzisothiazolylpiperazine incorporating potent D2 and 5-HT2A antagonist activity was investigated as an approach to a novel atypical antipsychotic agent. The in vitro profile of 8e from this series is a combination of D2 receptor affinity comparable to the typical antipsychotic agent haloperidol and a 5-HT2A/D2 ratio comparable to the atypical agent clozapine. In vivo 8e possesses activity consistent with an efficacious antipsychotic agent with less tendency to induce extrapyramidal side effects in man.
authors.affiliation: Central Research Division, Pfizer Inc., Groton, Connecticut 06340, USA.
authors.forename: H R
authors.initials: HR
authors.lastname: Howard
authors.forename: J A
authors.initials: JA
authors.lastname: Lowe
authors.forename: T F
authors.initials: TF
authors.lastname: Seeger
authors.forename: P A
authors.initials: PA
authors.lastname: Seymour
authors.forename: S H
authors.initials: SH
authors.lastname: Zorn
authors.forename: P R
authors.initials: PR
authors.lastname: Maloney
authors.forename: F E
authors.initials: FE
authors.lastname: Ewing
authors.forename: M E
authors.initials: ME
authors.lastname: Newman
authors.forename: A W
authors.initials: AW
authors.lastname: Schmidt
authors.forename: J S
authors.initials: JS
authors.lastname: Furman
authors.forename: G L
authors.initials: GL
authors.lastname: Robinson
authors.forename: E
authors.initials: E
authors.lastname: Jackson
authors.forename: C
authors.initials: C
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Morrone
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002375:Catalepsy / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D010716:Phosphatidylinositols / Q000037:antagonists & inhibitors / Q000378:metabolism; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D011224:Prazosin / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D012702:Serotonin Antagonists / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D014150:Antipsychotic Agents; D010716:Phosphatidylinositols; D010879:Piperazines; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D012702:Serotonin Antagonists; D013844:Thiazoles; D000661:Amphetamine; D003024:Clozapine; D001058:Apomorphine; D004298:Dopamine; D011224:Prazosin