Abstract

We have synthesized a series of spin-labeled derivatives of morphine and codeine and have used electron spin resonance spectroscopy to examine some of the interactions of these molecules. Animal studies were conducted to determine the relative analgesic potencies of these drugs. A series of expeniments was conducted in which one of the spin-labeled drugs was isolated from the brains of rats and ESR was used to show that enzymatic hydrolysis of the drug was a relatively slow process. These experiments indicate that the pharmacological effects of these drugs are due to the spin-labeled molecules and not to a hydrolysis product (morphine or codeine). ESR was also used to demonstrate that the spin-labeled drugs bind to isolated synaptic membrane preparations. These experiments indicate that ESR will be a valuable tool for the study of the interaction of spin-labeled analgesic drugs with membranes.