Intrathecal delivery of α2-adrenergic agonists produces an analgesic effect. However, hemodynamic side effects limit their clinical usage. To more fully characterize the effects on heart rate and arterial blood pressure of α2-adrenergic agonists, clonidine and tizanidine were injected intrathecally in conscious dogs. Both compounds produced a potent inhibition of thermal foot-withdrawal latencies at 1000 μg, which was blocked by the α2-adrenergic antagonist yohimbine. Tizanidine (250-500 μg) did not change heart rate. Clonidine (500-2000 μg) and tizanidine (1000-2000 μg) decreased heart rate. The tizanidine effect was inhibited by yohimbine and the α2/imidazoline antagonist idazoxan, as well as the parasympathetic blocker glycopyrrolate. No drug completely inhibited the clonidine-induced bradycardia. Clonidine had a biphasic effect on arterial blood pressure, a decrease at 500 μg and an increase at 2000 μg. Tizanidine decreased arterial blood pressure at all doses. The results indicate that, while the analgesic effects of both drugs are similar, the hemodynamic responses differ. While the decrease in heart rate with tizanidine is consistent with α2-adrenergic binding and vagal action, the bradycardia induced by clonidine is more complex. In addition, the increased arterial blood pressure with high doses of clonidine, which is suggestive of a peripheral vasoconstrictive effect, does not occur with tizanidine.
ASJC Scopus subject areas
- Anesthesiology and Pain Medicine