| Abstract
| - A series of novel 2-[(4-phenylpiperazin-1-yl)methyl]imidazoazines and aza-analogues were prepared andscreened at selected dopamine, serotonin, and adrenergic receptor subtypes. 2-Substituted imidazopyridinesand pyridazines presented high affinities and selectivities for D4 dopamine receptors. Whereas functionalexperiments indicated neutral antagonists or weak partial agonist effects for most of the target compounds,the 2-methoxyphenyl substituted 2-piperazinylmethylimidazopyridine 3c (PIP3EA) displayed substantialagonist efficacy in mitogenesis experiments and GTPγS binding tests, resulting in EC50 values of 3.0 (46%)and 4.5 nM (57%), respectively. Our D4 agonist 3c induced penile erection in vivo when administered torats. This effect was inhibited by L-745,870 a D4 selective antagonist, confirming the mechanistic pathway.
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