The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Aug 1990
Interaction of intrathecal morphine and ST-91 on antinociception in the rat: dose-response analysis, antagonism and clearance.
Physiological data suggest that the direct effect of spinal opiates as well as the activation of adrenergic bulbospinal pathways each results in a reduction in the gain of the stimulus response function in dorsal horn neurons. In its simplest form, this suggests the hypothesis that co-activation of spinal alpha2 and opioid receptors should be manifested as a synergistic interaction in which in its simplest form the net effect would be a product of the effect produced by either drug alone. To assess this hypothesis, rats were prepared with chronically implanted intrathecal (IT) catheters. ⋯ Confirmation of the synergistic nature of spinal opioid alpha 2 receptors was provided by the fact that IT injection of naloxone (90 nmol) or phentolamine (100 nmol) after IT injection of various combinations of morphine and ST-91 immediately and completely abolished the potentiating effect of the combination. The clearance of IT [3H]morphine from the thoracic and lumbar spinal cord was not changed in the presence of ST-91. These observations suggest a potent synergistic interaction between spinal mu and alpha 2 adrenergic receptor systems.