DL-四氢巴马汀对大鼠单胺的排空作用

DL-四氢巴马汀(THP)是中药延胡索的有效成分,具有镇静、安定、镇痛和温和降压等作用。本文用高压色谱并用电化学检测器法研究了THP对大鼠单胺代谢的影响。THP60mg/kg能降低三种单胺介质的含量:DA(-70%),NA(-50%),5-HT(-30%)。它们的酸性或中性代谢物HVA,DOPAC,MHPG-SO₄和5-HIAA含量显著升高(+200～300%)。而DA的甲基化代谢物3-甲氧基酪胺(3-MT)含量明显减少。DA酸性代谢物的升高和DA被COMT甲基化的代谢物3-MT的降低,皆表示DA被排空和导致DA能系统功能的低落。可以得出结论,THP是一个短效单胺排空剂。

DEPLETION OF MONOAMINES IN THE RAT BY DL-TETRAHYDROPALMATINE

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-SO₄ 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.