Abstract
Idazoxan potentiates spinal reflexes in the decerebrated rabbit, an effect that has been attributed to antagonism of tonic noradrenergic inhibition. It is now known that this drug has a higher affinity for I 2-imidazoline receptors than α 2-receptors. The roles of I 2-receptors in modulating transmission in spinal reflex pathways have been investigated using the selective ligands RX 821029 and RS-45041-190, and, as I 2-receptors are closely associated with monoamine oxidase (MAO), the MAO inhibitors pargyline and clorgyline. In decerebrated rabbits with an intact spinal cord, intrathecal doses of 5–365 μg (cumulative) of the I 2-ligands augmented, to 150–180% of pre-drug levels, the reflex responses of medial gastrocnemius motoneurones to electrical stimulation of the sural nerve, and significantly increased mean arterial blood pressure by approximately 10 mmHg over pre-drug values. Neither MAO inhibitor had significant effects on reflexes, but the highest dose of the MAO-A selective agent clorgyline (365 μg cumulative) caused a significant rise in blood pressure of 6 mmHg. Neither the I 2-ligands nor the MAO inhibitors prevented the further enhancement of reflexes or blood pressure by subsequent administration of the selective α 2-adrenoceptor antagonist RX 821002. In decerebrated, spinalized rabbits, intrathecal RS-45041-190 (60 μg, single dose) increased spinal reflex responses to 109% of pre-drug values, a significantly smaller effect than that seen in non-spinal preparations, and had no effect on blood pressure. These data show that imidazoline I 2-receptors can influence somatic and autonomic motor outflows. These effects should be taken into account when interpreting the spinal effects of imidazoline-based adrenoceptor-active drugs.
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