Neuroleptic piperazinyl-dibenzo-azepines. Chemistry and structure-activity relationships

The chemistry and the molecular and physicochemical properties of the 11-piperazinyl derivatives of dibenz[b,f][1,4]-oxazepines and -thiazepines and of dibenzo[b,e][1,4]diazepines as well as those of the 6-piperazinyl-morphanthridines are reviewed. The physicochemical parameters sigma, pK, eta, RM and surface pressure are considered in relation to each other and in relation to two pharmacological effects, namely apomorphine antagonism and cataleptic activities. The influence of substituents, bridging moiety and basic side chain on structure-activity are discussed. Finally, the dibenzodiazepine derivative clozapine, which differs markedly from the classical neuroleptics in its biochemical, pharmacological and clinical properties and represents a new type of antipsychotic agent, is discussed.