alexa Different effects of enantiomers of tetrahydropalmatine on dopaminergic system.


Journal of Addiction Research & Therapy

Author(s): Jin GZ, Xu SX, Yu LP

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Abstract 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 (Ki = 0.2 microM). Neither d-THP nor reserpine showed such an effect even at concentrations higher than 100 or 1000 microM. Based on the fact that the presynaptic DA receptors take part in feed-back regulation on tyrosine 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 25 mg/kg, naught at 50 mg/kg, and a 91\% increment at 100 mk/kg, which was less than that of l-THP at 5 mg/kg. Moreover, measured by pulse voltammetry, DOPAC level in the striatum was raised by 88 or 190\% at 2.5 or 10 mg/kg respectively. By means of spectrofluophotometry, l-THP at 50-100 mg/kg reduced DA level by 24-26\%. However, the DA content reduction induced by d-THP is much more dose-dependent. At a small dose (10 mg/kg), d-THP predominantly reduced the DA level but left 5-HT and NA level unaffected. It caused an 80\% reduction of DA at 100 mg/kg. From the above findings, it might be concluded that l-THP is a DA receptor antagonist, while d-THP is probably a DA depletor.
This article was published in Sci Sin B and referenced in Journal of Addiction Research & Therapy

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