Pharmacological profiles of three new, potent and selective dopamine receptor agonists: N-0434, N-0437 and N-0734

Abstract

A series of new dopamine (DA) receptor agonists, of the 2-aminotetralin group, i.e. N-0434, N-0437 and N-0734 were investigated in both in vivo and in vitro pharmacological test systems. In vivo, the reversal of the γ-butyrolactone-induced increase in rat central DOPA biosynthesis rate was taken as a measure of presynaptic activity. In addition, the homovanillic acid (HVA) decrease, after intraperitoneal and after oral administration of the drugs was also taken as a measure of presynaptic activity. Postsynaptic activity was measured in two behavioural models, i.e. reserpine reversal and stereotypy induction. The effects of these drugs on noradrenaline and dopamine turnover (α-MpT method) were studied in addition. The displacement of [ 3H]N,N-dipropyl-5,6-dihydroxy-2-aminotetralin ([ 3H]DP-5,6-ADTN) binding to rat striatal homogenates was studied in vitro. The results indicate that all three compounds are potent and selective DA agonists that lack significant α 2 activity. Because of its long duration of action and high oral activity, N-0437 seems to be a most promising candidate for further evaluation for possible therapeutic use.