Mechanism of analgesic action of mesaconitine. I. Relationship between analgesic effect and central monoamines or opiate receptors

The contribution of the central monoamines and the opiate receptor to mesaconitine (MA)-induced analgesia was investigated by means of pharmacological and neurochemical methods in which morphine (Mor) was used for comparison. The analgesic action of MA (i.c.) determined by the acetic acid-induced writhing method and the tail flick method was dose-dependent, indicating that its activity is elicited through the central nervous system. MA-induced analgesia was decreased by alpha-methyl-p-tyrosine (alpha-MT), 6-hydroxydopamine, diethyldithiocarbamate, disulfiram and reserpine, and increased by methamphetamine and norepinephrine (NE). The mode of action of MA was similar to that of Mor except for the results obtained upon combined administration with 1-dopa, dopamine, alpha-MT or chemicals related to 5-hydroxytryptamine. In addition, MA promoted the alpha-MT-induced decrease in NE levels in hippocampus, medulla oblongata plus pons and spinal cord. Levallorphan did not affect the analgesic activity of MA, showing that its activity is not mediated via the opiate receptors. Consequently, it is concluded that the analgesic activity mediated by MA is closely related to responses involving the central catecholaminergic system, in particular, the noradrenergic system.