Structural and steric requirements for ?-phenethylamines as agonists of the noradrenergic cyclic AMP generating system in the rat limbic forebrain

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Abstract
The present studies were undertaken to assess the structural and steric requirements for β-phenethylamines as agonists of the noradrenergic cyclic AMP generating system in slices of the rat limbic forebrain. Significant agonist activity of β-phenethylamines requires a β-3,4-dihydroxyphenethylamine with a β-hydroxyl group in the R configuration. Thus, dopamine did not stimulate the system at concentrations up to 10−3 M. Moreover, β-hydroxyphenethylamines without a 3,4-catechol group (octopamine, phenylephrine, p-hydroxynorephedrine, metaraminol and methoxamine)-though exerting α-agonist activity in peripheral tissues-lack agonist activity in this particular cyclic AMP generating system. The effects of (R)-norepinephrine and (R)-isoproterenol at maximal concentrations were not additive. The results lend further support to the view that the cyclic AMP generating system in slices of the limbic forebrain is part of a norepinephrine receptor coupled adenylate cyclase system with a subpopulation of receptors that are β in nature.

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