HIGH-AFFINITY PARTIAL AGONIST IMIDAZOL[1,5-A]QUINOXALINE AMIDES, CARBAMATES, AND UREAS AT THE GAMMA-AMINOBUTYRIC-ACID-A BENZODIAZEPINE RECEPTOR COMPLEX

A series of imidazo[1,5-alpha]quinoxaline amides, carbamates, and urea s which have high affinity for the gamma-aminobutyric acid A/benzodiaz epine receptor complex was developed. Compounds within this class have varying efficacies racing from antagonists to full agonists. However, most analogs were found to be partial agonists as indicated by [S-35] TBPS and Cl- current ratios. Many of these compounds were also effecti ve in antagonizing metrazole-induced seizures in accordance with antic onvulsant and possible anxiolytic activity. Selected quinoxalines disp layed limited benzodiazepine-type side effects such as ethanol potenti ation and physical dependence in animal models. Dimethylamino urea 41 emerged as the most interesting analog, having a partial agonist profi le in vitro while possessing useful activity in animal models of anxie ty such as the Vogel and Geller assays. In accordance with its partial agonist profile, 41 was devoid of typical benzodiazepine side effects .