Characteristics of Antinociception Induced by Noncatecholic Phenylethylamine Derivatives: The Involvement of Alpha-2-Adrenoceptors.

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Characteristics of the antinociceptive action of phenylethylamine derivatives, amphetamine, β-phenylethylamine (PEA) and β-hydroxyphenylethylamine (OHPEA), were examined. The antinociception induced by PEA derivatives was enhanced by intracisternal injection of norepinephrine or clonidine and attenuated by intracisternal injection of phentolamine or yohimbine, but was not affected by intracisternal injection of prazosin in the mouse hot plate method. PEA derivatives induced a contraction of the rat vas deferens, and this contraction by PEA derivatives was attenuated by the application of phentolamine. The contractions induced by PEA or OHPEA in the reserpinized vas deferens were much smaller than those in the normal one. PEA derivatives inhibited the electrical stimulation-evoked contractions of the vas deferens, and the inhibition by PEA derivatives was reversed by the application of yohimbine. These findings indicate that PEA derivatives may induce the antinociception as a result of stimulating the α2-adrenoceptors. The stimulation of α2-adrenoceptors by PEA derivatives may result from the release of endogenous norepinephrine and/or from direct action on the α2-adrenoceptors.