Beta 2-adrenoceptor influences on the alpha 1- and alpha 2-mediated vasoconstriction induced by phenylpropanolamine and its two component enantiomers in the pithed rat.

Phenylpropanolamine (PPA, (+/-)-norephedrine) is commonly found in appetite suppressants and nasal decongestants. Within the cardiovascular system of the pithed rat, the drug and its two component enantiomers ((-)- and (+)-norephedrine) are largely direct-acting agonists. The interaction between simultaneous alpha 1-, alpha 2- and beta 2-adrenoceptor mediated effects of the drug and its two enantiomers have been examined using the cardiovascular system of the pithed rat. On all adrenoceptors tested the potency was (-)- greater than (+/-)-, greater than (+)-norphedrine. The alpha 1- and alpha 2-mediated pressor responses of each were enhanced in the presence of the beta 2-adrenoceptor antagonist, ICI 118,551, and diminished in the presence of the selective beta 2-adrenoceptor agonist salbutamol. It is concluded that each form of the drug possesses the intrinsic ability to interact with the alpha 1-, alpha 2- and beta 2-adrenoceptors in the system used and that the interaction with those adrenoceptors determines the net increase in diastolic blood pressure that follows the intravenous administration of the compounds. These findings have a bearing on the recent controversy regarding the use of beta-blocking agents in the treatment of overdosage of the drug.