Asunto(s)
Estimulantes del Apetito/química , Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Ghrelina/antagonistas & inhibidores , Hidrazinas/química , Hidrazinas/farmacología , Receptores de Ghrelina , Animales , Estimulantes del Apetito/farmacocinética , Estimulantes del Apetito/farmacología , Dicroismo Circular , Femenino , Ghrelina/metabolismo , Hidrazinas/farmacocinética , Ligandos , Estructura Molecular , Ratas , Ratas Sprague-Dawley , Receptores de Ghrelina/antagonistas & inhibidores , Relación Estructura-ActividadAsunto(s)
Hidrazinas/química , Receptores de Ghrelina/antagonistas & inhibidores , Línea Celular , Evaluación Preclínica de Medicamentos , Trastornos de Alimentación y de la Ingestión de Alimentos/tratamiento farmacológico , Humanos , Hidrazinas/síntesis química , Hidrazinas/uso terapéutico , Receptores de Ghrelina/metabolismo , Relación Estructura-ActividadRESUMEN
Since the initial observations linking 5-HT to psychiatric illness, evidence for a role of 5-HT and, in particular, a decreased brain serotonergic function in the pathology of a plethora of related disorders, has grown. However, it is the role of 5-HT in the pathogenesis of anxiety disorders and depression and the mechanism of action of antidepressants which has received the most attention. Thus enhanced serotonergic neurotransmission has become one of the unifying mechanisms of action of modern day antidepressants/anxiolytics such as monoamine oxidase inhibitors, tricyclic antidepressants, and serotonin reuptake inhibitors. Interestingly all of these treatments are associated with a delay to therapeutic efficacy and in some cases treatment resistance, despite immediate enhancements in serotonergic neurotransmission. The postulated reason for this is the need for temporal neuroplastic changes in the control of serotonergic neurotransmission, and more specifically changes in 5-HT(1) autoreceptor function. Thus significant research has gone into pharmacologically targeting these 5-HT(1) autoreceptors as a means of augmenting the efficacy of current therapeutic mechanisms. Here we will review the rationale behind the various augmentation strategies adopted and the progress made in identifying novel therapeutics for conditions such as depression and anxiety disorders.