The objectives of the proposed research are to utilize immunological methods to study the molecular basis for the pharmacologic activity of narcotic analgesics and to investigate the effect of specific antisera on the biologic effects of these drugs. Derivatives of morphine and other opioids will be prepared and chemically characterized. These compounds will be conjugated with bovine serum albumin and the conjugates used to immunize rabbits. Antibody levels will be determined using a modification of Farr's ammonium sulfate method. Antibody affinity will be measured by this technique as well as by equilibrium dialysis. Specificity of antibody reactivity will be evaluated by determining the ability of various unlabeled opioids to inhibit the binding of the opioid used for immunization. Antibody of defined affinity and characterized specificity will be obtained by affinity chromatography using columns of sepharose conjugated with appropriate opioid derivatives. These antibody fractions will be used to study the placental transfer of meperidine and methadone and to characterize some aspects of the metabolism of these drugs. The concentrations in the cord serum of the infants will be correlated with the extent of observed depression. Such purified antibodies also should provide more specific reagents for assay methods to detect individual opioids and possibly distinguish between the opioid and metabolic products. These antisera will also be used to investigate the pharmacologic mechanisms of opiate action, for determining affinity constants of tissue receptors and for studying the effects of antibodies on the biological activities of opioids using inhibition of electrically induced contraction of guinea pig ileum and drug seeking behavior of rhesus monkeys as the major bioassays.
NIH ExPorter
NIH ExPorter