Production of catalepsy and depletion of brain monoamines by a butyrophenone derivative.
1 The cataleptic and monoamine-depleting effects of a butyrophenone derivative (4'-fluoro-4-[[4-(p-fluorophenyl)-3-cyclohexen-1-yl]-amino]-butyrophenone hydrochloride, U-32, 802A) were studied in rats and mice and compared with those of tetrabenazine. 2 Catalepsy was evaluated by means of a modified grid test which allowed the repetition of the test in the same animal several times without affecting the results. Both drugs produced a dose-related cataleptic state of similar time course. 3 Like tetrabenazine, U-32, 802A induced a large reduction in the content of 5-hydroxytryptamine, dopamine and noradrenaline in different parts of the brain, with a concomitant elevation in the metabolites 5-hydroxyindol-3-yl acetic acid and homovanillic acid. The time courses of the catalepsy and the reduction in brain monoamines were very similar. 4 The activity of U-32, 802A suggested that the drug, although chemically a butyrophenone, might act primarily at the presynaptic organelle for storage of monoamines in a way similar to tetrabenazine.
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001831:Body Temperature / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002090:Butyrophenones / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013747:Tetrabenazine / Q000494:pharmacology
D001679:Biogenic Amines; D002090:Butyrophenones; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid; D013747:Tetrabenazine