Stimulation of presynaptic peripheral dopamine receptors (DA2) produces sympathoinhibition resulting in hypotension. Postsynaptic peripheral dopamine receptor (DA1) activation subserver's vasodilation and diuresis. The design and synthesis of highly specific agonists for peripheral dopamine receptors have evolved into a new approach for the control of hypertension. The action of N, N-di-n-propyldopamine on peripheral dopamine receptors resulting in reduced blood pressure and reduced heart rate has stimulated the synthesis of similar compounds. The potential clinical application of these substituted (aralkyl) phenethylamines is a topic of current interest. This research project proposes to (a) synthesize and characterize a series of N-aralkyl derivatives of phenethylamine and related compounds, (b) evaluate the effectiveness of these compounds on peripheral dopamine receptors utilizing regional blood flow measurements (pulsed Doppler flowmeter) in rats and (c) further characterize the peripheral dopamine receptors using chemical probes (i.e., heavy metals). Synthetic scheme development will be a major thrust of this investigation. Regional blood flow measurements will be performed in conscious and anesthetized animals for peripheral dopamine receptor activity. Chemical probing of the receptors will also use the regional blood flow measurement technique. The proposed research is significant because it may provide new series of antihypertensive agents and additional information about peripheral dopamine receptors.
