3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents.
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.
Howard
H R
HR
Central Research Division, Pfizer Inc., Groton, Connecticut 06340, USA.
Lowe
J A
JA
Seeger
T F
TF
Seymour
P A
PA
Zorn
S H
SH
Maloney
P R
PR
Ewing
F E
FE
Newman
M E
ME
Schmidt
A W
AW
Furman
J S
JS
Robinson
G L
GL
Jackson
E
E
Johnson
C
C
Morrone
J
J
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*
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