COMPARISON OF TETRAHYDROPALMATINE, TETRABENAZINE AND RESERPINE IN MONOAMINE DEPLETING ACTION

dl-Tetrahydropalmatine (dl-THP), a tetrahydroisoquinoline alkaloid, was found to lower monoamines and increase their acidic metabolites in rat brain and considered to be a short acting monoamine depletor. In the present studies, dl-THP (60mg/kg), in combination with reserpine (1.5mg/kg), caused a further significant decrease in rat brain levels of NA and DA to 15% and 5% of the normal values respectively, compared to 40% and 25%, respectively, after reserpine alone, dl-THP also potentiated the action of reserpine in depleting scrotonin. On the contrary, pretreatment with tetrabenazine (50 mg/kg) partially antagonized reserpine in decreasing the brain levels of monoamines. These results imply that the site of action of THP on the storage mechanism of synaptic vesicle seems to distinguish from that of tetrabenazine though both drugs are short-term monoamine depletors. In addition, dl-THP showed no effect on Na⁺K⁺-ATPase and Mg²⁺-ATPase activities. In this aspect, THP is different from reserpine, dl-THP at the concentration of 10^-4 mol/L was found to evoke rhythmic contraction of isolated guinea-pig vas deference and not antagonized by phentolamine, propanolol, haloperidol, atropine or cyproheptadine. In vivo, dl-THP, like reserpine, at relatively large dose lowered the body temperature of rats.