DIFFERENT EFFECTS OF ENANTIOMERS OF TETRAHYDROPALMATINE ON DOPAMINERGIC SYSTEM

Tetrahydropalmatine (THP) has two enantiomers with different effects on the brain dopaminergic system. Using [~3H]spiperone for DA receptor binding assay, it was found that l-THP had an affinity to DA receptors (K_1=0.2μM). Neither d-THP nor reserpine showed such an effect even at concentrations higher than 100 or 1000μM. Based on the fact that the presynaptic DA receptors take part in feed-back regulation on tyrosiue hydroxylase activity, DOPA accumulation could be observed in rat striatum after injection of benserazide. A small dose of l-THP (2.5, 5, 10 mg/kg, ip.) caused an elevation of DOPA level by 49—282% versus the control value, and could reverse the decrease of DOPA level induced by apomorphine, a DA receptor agonist. On the contrary, d-THP displayed a biphasic effect on DOPA level, slight decrement (26—37%) at 10 and 25mg/kg, naught at 50mg/kg, and a 91% increment at 100 mk/kg, which was less than that of l-THP at 5mg/kg. Moreover, measured by pulse voltammetry, DOPAC level in the striatum     

四氢巴马汀旋光异构体对脑内多巴胺能系统的不同药理作用

本文以[~3H]-spiperone为配基,证实ι-THP与脑内DA受体有亲和力(K_i=0.2μM),而d-THP无亲和力(K_i>0.1mM)。小剂量ι-THP(2.5—10mg/kg)能增加尾核内TH酶活力,加速ι-dopa生物合成,又能拮抗去水吗啡抑制ι-dopa的生物合成,表明它们在突触前DA受体水平相拮抗;大剂量d-THP(100mg/kg)略能增强TH酶活力,增加ι-dopa的含量,但ι-THP比它强20—50倍,并且此作用不可能由于d-THP阻滞DA受体所引起。应用DPV法和荧光测定法,证实小剂量ι-THP能使尾核内DOPAC和HVA增加数倍。上述资料均表明ι-THP是DA受体拮抗剂。d-THP(25mg/kg)明显减少DA含量,增为100mg/kg时,D减少80％。大剂量的d-THP能使脑内5-HT和NA约减少20％,仅为DA影响的1/4。所以,d-THP较专一地降低DA含量。大剂量的ι-THP对脑内5-HT和NA的含量无明显影响,虽稍减DA含量,可能由于阻滞突触前DA受体,反馈性增强释放DA的缘故。