Profile of in vitro binding affinities of neuroleptics at different rat brain receptors: cluster analysis comparison with pharmacological and clinical profiles.
A series of 21 neuroleptics with different chemical structures (phenothiazines, thioxanthenes, dibenzodiazepines, butyrophenones, benzamides, etc.) was examined for their in vitro interactions with 12 neurotransmitter binding sites in the rat brain (alpha- and beta-noradrenergic, dopaminergic, muscarinic, serotoninergic, histaminic, and opioid receptors, calcium channels, and serotonin uptake binding sites). The biochemical profile obtained from the binding data was compared with reported pharmacological and clinical profiles for this class of compounds by cluster analysis. Cluster analysis on binding data classified the compounds in three main subgroups: benzamides, compounds with an affinity mainly for DA2 and 5-HT2 receptors and inactive at muscarinic receptors, and compounds with a high affinity for alpha 1-adrenergic receptors and muscarinic receptors. The main subgroups resulting from cluster analysis of previously published pharmacological and clinical data for neuroleptics contain compounds common to the present study, with some correlations. The results extend previous observations that a complete binding profile corresponds to the pharmacological and clinical profile of this class of compounds.
Testa
R
R
Recordati SpA, Research Laboratories, Milan, Italy.
Abbiati
G
G
Ceserani
R
R
Restelli
G
G
Vanasia
A
A
Barone
D
D
Gobbi
M
M
Mennini
T
T
D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000187:drug effects* / Q000378:metabolism
D014150:Antipsychotic Agents; D011955:Receptors, Drug