N,N-di-n-Propyl-7-hydroxy-2-aminotetralin (DP-7-AT), a Selective Dopamine Autoreceptor Agonist?

Abstract

We have recently provided evidence that in a series of N,N-disubstituted 2-aminotetralin derivatives, 5-OH substitution is essential for high stimulating potency at postsynaptic dopamine (DA) receptors and that derivatives that lack this substitution pattern possess high selectivity for DA autoreceptors (Van Oene et al., 1984). These conclusions have been based upon the results obtained using reversal of the γ-butyrolactone-induced increase in rat striatal DA synthesis rate as a measure of in vivo stimulating potency at DA autoreceptors, and reversal of the reserpine-induced immobility of mice as a measure of in vivo stimulating potency at postsynaptic DA receptors. Now a comparison is made between the most selective DA autoreceptor agonist of the series, DP-7-AT, and its nonselective positional isomer DP-5-AT. These two compounds were found to have qualitatively similar effects (parallel dose-response curves) in the DA autoreceptor test model in both rats and mice, being half-maximally effective at doses of 75 and 120 nmol/kg i.p. (DP-5-AT) and 410 and 350 nmol/kg i.p. (DP-7-AT) in these species, respectively.