RESUMEN
Immunization of a rabbit with a racemic mixture of (+/-)-oxaprotiline, conjugated to bovine serum albumin, resulted in two antibody populations with affinity constants 1.5 x 10(9) and 2.5 x 10(6) M-1. Both populations showed a higher affinity for the (-)-isomer than for the (+)-isomer of the drug. Both stereoisomers of the drug were immunogenic in mice, but only the (-)-isomer was recognized with high affinity. Somatic fusion of the spleen of a mouse, immunized with the (-)-isomer yielded 12 hybridomas secreting monoclonal anti-oxaprotiline antibodies. Five of these monoclonal antibodies (MAbs) recognized both isomers, four bound more specifically to the (-)-isomer, one recognized the (+)-isomer and two were specific for the coupling arm. One of the MAbs was further analyzed to gain insight into the structural features of the drug involved in antibody recognition. This analysis suggested that the stereospecific recognition of oxaprotiline could be directly linked to the position of the hydroxyl group on the asymmetric carbon.
Asunto(s)
Antracenos/inmunología , Antidepresivos/inmunología , Reacciones Antígeno-Anticuerpo , Maprotilina/inmunología , Animales , Anticuerpos/inmunología , Anticuerpos Monoclonales/biosíntesis , Afinidad de Anticuerpos , Maprotilina/análogos & derivados , Ratones , Ratones Endogámicos BALB C , Modelos Moleculares , Conejos , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
Psychological states such as bereavement and depression have been associated with suppression of the immune response. The authors present a pilot study utilizing the anti-depressant, maprotiline hydrochloride (Ludiomil) to determine its effects on the mental depression and immune reactions of T&B lymphocytes in patients with neurotic depression (dysthymic disorder by DSM III). Hope scores, derived from the content analysis of verbal samples, and Beck depression scores were examined as they covaried with various indices of immune response before and 3 months after the patients were administered either maprotiline or no anti-depressant medication. Although the study did not provide definitive findings regarding improved response following treatment of depressed patients with maprotiline hydrochloride, it did suggest further avenues of research for investigation.