Relevance of sedative-tranquilizing effect of l-tetra-hydropalmatine to brain monoaminergic neurotransmitters

l-Tetrahydropalmatine (l-THP) possessed a marked tranquilizing effect. The brain levels of NA and 5-HT were hardly influenced by l-THP 100 mg/kg, and the striatal level of DA was slightly reduced (P>0.05). But reserpine reduced the levels of 5-HT, NA and DA markedly. Hence l-THP, in contrast with the action of reserpine, did not deplete the stored monoamines. The stereotyped behavior induced by apomorphine or benserazide +l-dopa +de-prenyl in rats and the rotational activity induced by apomorphine or amphetamine in 6-OH-DA lesioned rats were all anta-gonized by l-THP (50 mg/kg) as halope-ridol did. Thus l-THP blocked post-synap-tic DA receptor. In rats, the hyperactivi-ty evoked by p-chloro-N-methylamphe-tamine (PCMA). scopolamine or atropine was antagonized by l-THP 10-15 mg/kg. l-THP did not antagonize the convul-sions produced by picrotoxin and bicucul-line which are the selective blocking a-gents of GABA receptor. In contrast with l-THP, AOAA and diazepam antagonized the convulsion effectively. It is concluded that the blockade of DA-receptor is an important mechanism of the tranquilizing action of l-THP, not involving the depletion of stored monoa-mines or augmentation of GABA function.