Asunto(s)
Antidepresivos de Segunda Generación , Piperazinas , Piperidinas , Esquizofrenia/tratamiento farmacológico , Animales , Antidepresivos de Segunda Generación/efectos adversos , Antidepresivos de Segunda Generación/farmacología , Antidepresivos de Segunda Generación/uso terapéutico , Trastornos del Conocimiento/tratamiento farmacológico , Antagonistas de los Receptores de Dopamina D2 , Método Doble Ciego , Descubrimiento de Drogas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Piperazinas/efectos adversos , Piperazinas/farmacología , Piperazinas/uso terapéutico , Piperidinas/efectos adversos , Piperidinas/farmacología , Piperidinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Antagonistas del Receptor de Serotonina 5-HT2 , Resultado del TratamientoRESUMEN
Two major metabolites in humans of blonanserin, 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta-[b]pyridine (code name AD-5423), were synthesized. The first, 7-hydroxylated AD-5423, was synthesized through a four-step process starting from 4-fluorobenzoylacetonitrile (1), and the second, 8-hydroxylated AD-5423, a nine-step process also from 1. The optical resolution, structures, and receptor binding properties of the metabolites were documented.
Asunto(s)
Antipsicóticos/síntesis química , Piperazinas/síntesis química , Piperidinas/síntesis química , Antipsicóticos/metabolismo , Antipsicóticos/farmacología , Humanos , Microsomas Hepáticos/metabolismo , Piperazinas/metabolismo , Piperazinas/farmacología , Piperidinas/metabolismo , Piperidinas/farmacología , Receptor de Serotonina 5-HT2A/química , Receptor de Serotonina 5-HT2A/metabolismo , Receptores de Dopamina D2/química , Receptores de Dopamina D2/metabolismo , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
Animal models of psychiatric disorders are indispensable tools to gain insights into neural mechanisms underlying these disorders and to assess potential therapeutic actions of novel compounds in preclinical settings. However, it is difficult to establish appropriate animal models for these disorders because there is no proof on whether or not what occurs in the animal brain is comparable to what occurs in the human brain. The initial development of animal models of psychiatric disorders is often based on "face validity" as reflected in the similarity of behavioral signs and symptoms observed in humans and animal and subsequently based on "construct validity" as measured by strong correlation in behaviors and neural events between the animal model and patients of the disorder. The practical value of such animal models is reflected ultimately in their "predictive validity" in predicting the therapeutic efficacy of new treatments for psychiatric disorders. The present review will focus on animal models of schizophrenia and depression by the use of mainly environmental stress and pharmacological treatments, which are expected to induce signs and symptoms analogous to those of patients with such disorders.
