Enantiomerically pure aminoindolizines: bicyclic ergoline analogues with dopamine autoreceptor activity.

The development of drugs which stimulate selectively the prejunctional dopamine receptor has become a major challenge in recent years1,2), These autoreceptor agonists decrease synthesis and release of dopamine (OA), Thus, the symptoms of schizophrenia originated from dopamine hyperactivity in the mesolimbic system should be reduced. On the other hand, it has been shown that OA autoreceptor agonists fail to reveal classical OA antagonist side effects like catalepsy, when given to animals3). Since the highly sensitive OA autoreceptor is assumed to resemble the postsynaptic 0-2 receptor4•5), we planned to develop novel autoreceptor agonists by specific structural modifications of known 0-2 agonists. One