DEPLETION OF MONOAMINES IN THE RAT BY DL-TETRAHYDROPALMATINE
LIU Guo-qing, Sergio Algeri~* and Silvio Garattini~* (Department of Pharmacology, Nanjing College of Pharmacy) ~* "Mario Negri" Institute for Pharmacological Research, Milan
DL-Tetrahydropalmatine (THP)is an active principle isolated from Corydalis ambigua, which was reported to have analgesic, sedative, tranquilizing, bradycardia and mild hyp0tensive effects. The drug′s biochemical effects on the rat monoaminergic neuronal system were studied by high performance liquid chromatography coupled with electrochemical detection. It was found that THP (60 mg/kg) depleted all three transmitters: DA (—70%), NA (—50%), and 5-HT (—30%). There was an increase in their acidic and neutral metabolites: HVA and DOPAC for DA, MHPG-SO_4 for NA and 5-HIAA for 5-HT. However, methylated product of DA 3-methoxytyramine (3-MT), was lowered significantly. 3-MT is known to be produced by the release of DA from prejunctional terminals into the cleft, where it is methylated by COMT. The reduction of 3-MT and increase Of HVA and DOPAC indicate a reduction of nerve impulse flow in dopaminergic axons. These effects of THP appear to be similar to those reported for reserpine-like compounds such as tetrabenazine. Though THP and tetrabenazine showed similar actions, these drugs differ in some respects: the former exhibited analgesic activity and appeared to have a shorter-lastirrg action on monoamines than the latter.A working hypothesis has been put forward that the tranquilizing action and catalepsy induced by THP seemed to be correlated with the depletion of DA in the limbic area and striatum respectively. NA in the heart also dropped markedly which may be related to the mild hypotension and bradycardia caused by THP in animals. All these biochemical data suggest that THP should be considered a shortlasting monoamine depleter.