Monoaminergic involvement in the pharmacological actions of buspirone.
Buspirone, MJ-13805 and MJ-13653 did not produce a '5-hydroxytryptamine (5-HT) syndrome' in rats at doses up to 20 mg kg-1. These drugs were very weak 5-HT uptake blockers (IC50 much greater than 10 microM) compared to drugs such as chlorimipramine. These drugs did not inhibit either monoamine oxidase (MAO)-A or MAO-B. The Ki values for these agents as inhibitors of [3H]-5-HT and [3H]-ketanserin binding to rat frontal cortex or hippocampal membranes were in the microM range, well above the brain concentrations achieved after an oral dose of 25 mg kg-1. Parenterally administered buspirone blocked apomorphine-induced stereotypy, inhibited the 5-HT syndrome elicited by 5-methoxy-N,N-dimethyltryptamine, and delayed the onset of p-chloroamphetamine induced behaviours.
Skolnick
P
P
Weissman
B A
BA
Youdim
M B
MB
D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism*; D002065:Buspirone / Q000031:analogs & derivatives; D004298:Dopamine / Q000502:physiology; D007650:Ketanserin; D008297:Male; D008732:Methoxydimethyltryptamines / Q000037:antagonists & inhibitors; D008995:Monoamine Oxidase / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D010880:Piperidines / Q000378:metabolism; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D010133:p-Chloroamphetamine / Q000037:antagonists & inhibitors
D008732:Methoxydimethyltryptamines; D010879:Piperazines; D010880:Piperidines; D011619:Psychotropic Drugs; D011743:Pyrimidines; D012701:Serotonin; D010133:p-Chloroamphetamine; D007650:Ketanserin; D008995:Monoamine Oxidase; C037921:1-(2-pyrimidinyl)piperazine; C039979:gepirone; D001058:Apomorphine; D002065:Buspirone; D004298:Dopamine