PRODUCTION OF CATALEPSY AND DEPLETION OF BRAIN MONOAMINES BY A BUTYROPHENONE DERIVATIVE

Abstract

The cataleptic and monoamine‐depleting effects of a butyrophenone derivative (4′‐fluoro‐4‐[[4‐(p‐fluorophenyl)‐3‐cyclohexen‐l‐yl]‐amino]‐butyrophenone hydrochloride, U‐32, 802A) were studied in rats and mice and compared with those of tetrabenazine. 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. 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. 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.