Abstract
Tramadol is a clinically-used, orally-active drug which is considered to act as an analgesic in the CNS. In order to provide a cellular basis for this action, we examined a current response induced by a tramadol metabolite, mono-O-dimethyl-tramadol (M1), in substantia gelatinosa neurons of adult rat spinal cord slices by using the whole-cell patch-clamp technique. In 41% of the neurons examined, superfusing M1 induced an outward current at a holding potential of -70 mV. M1 current hardly declined and persisted for > 30 min after its washout. The M1 current reversed its polarity at a potential which is close to the equilibrium potential for K+. This M1 current correlated in amplitude with current produced by μ-opioid receptor agonist DAMGO in the same neuron, and suppressed in amplitude in the presence of μ-opioid receptor antagonist CTAP but not α2-adorenoceptor antagonist yohimbine. The amplitude of the M1 response, relative to that of the DAMGO response, exhibited an EC50 value of 300 μM. We conclude that M1 produces a persistent hyperpolarization by activating μ-opioid receptors in adult rat substantia gelatinosa neurons. This could contribute to at least a part of pain alleviation produced by tramadol. [Jpn J Physiol 55 Suppl:S148 (2005)]
