Pharmacological analysis of the mechanism of action of phenthiazamine, a piscine anesthetic.

Phenthiazamine was developed by Sekizawa et al. as a centrally acting anesthetic for fish. Frog sympathetic ganglion was used as a model to elucidate the mechanism of its anesthetic action. The positive ganglionic potential was enhanced immediately after application; then, the potential and the late negative ganglionic potential were markedly reduced by an anesthetic concentration of this compound. The hyperpolarization caused by 1 mM dopamine was enhanced by phenthiazamine. This enhancement of dopamine hyperpolarization and of the positive ganglionic potential may coincide with the fact that cyclic adenosine monophosphoric acid (cAMP) phosphodiesterase was inhibited by the compound as shown in our previous paper. Guinea-pig ileum contraction elicited by electrical field stimulation and by dimethyl-phenyl-piperadinium (DMPP) was reduced by a similar concentration of this compound, while the contraction elicited by acetylcholine and methacholine was not inhibited. The inhibition of contraction elicited by electrical field stimulation and DMPP may thus due to inhibition of acetylcholine release by this compound. The inhibition of ileum contraction by this compound was reversed by higher doses of Ca2+ (5.5 mM). The time required to reduce the positive ganglionic potential in the sympathetic ganglion by phenthiazamine was prolonged in the presence of higher concentrations of Ca2+. The Ca2+-dependent action potential of guinea-pig ureter was reduced by this compound, whereas it did not affect the Na+-dependent action potential.