The Ideal Antipsychotic: Hybrid between Typical Haloperidol And the Atypical Clozapine Antipsychotic

Abstract

The differences in types of psychoses, the suboptimal therapeutic response of psychotic individuals to antipsychotics, the variation of the therapeutic effects of the same antipsychotic on different individuals with the same disease, resistance to treatment, relapses despite completing a course of antipsychotic treatment, and the broad spectrum of side-effects of antipsychotics including the most recently designed ones, are pivotal factors necessitating the discovery of new antipsychotic agents. These should be therapeutically potent, efficient in monotherapy and devoid of known dangerous adverse effects that antipsychotics are blamed for. In this comparative review we elucidate two antipsychotic drugs, namely haloperidol and clozapine (typical and atypical antipsychotic agents, respectively) and discuss both their advantages and disadvantages. Because the pathogenesis of psychoses is not yet fully understood, and the prevention of psychoses is almost impossible rather being a myth, the search for the so called ideal, or the near-ideal, antipsychotic agent will continue. Based on this we propose the design of a “hybrid structure” having the desired properties of haloperidol and clozapine, with the intention being to find an optimal antipsychotic agent that exerts efficient therapeutic effects against both positive and negative symptoms of psychosis causing least possible side effects, such as in monotherapy.