D-L-tetrahydropalmatine as monoamine depletor.

D-L-Tetrahydropalmatine (THP), an alkaloid found in the plants of the Carydalis species, has been used as a non-narcotic analgesic and immediate or short-acting hypnotic. The drug's biochemical effects on the rat monoaminergic neuronal system were studied and the findings are presented here. THP's effects on concentrations of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) were determined. In all cases the drug caused a depletion of these transmitters. DA was most markedly affected by treatment (-70%), followed by NA (-50%) and 5-HT (-30%). In parallel with the reduced concentrations of the transmitters there was an increase in their acid and neutral metabolites: HVA and DOPAC for DA, 5HIAA for 5-HT and MHPG-SO4 for NA, indicating that THP increases the release of the monoamines. The concentration of 3-methoxytyramine, an extraneuronal metabolite of DA, was, however, reduced suggesting that the observed increase in metabolism is only an intraneuronal phenomenon and that the release of the neutotransmitter is actually impaired. The effect of THP on the peripheral adrenergic system was also determined. NA stores in heart sympathetic nerves were depleted, but the drug had no effect on the adrenaline content of adrenal glands. The biochemical action of THP seems, therefore, to be similar to that of reserpine-like drugs.