Blood pressure changes after intrathecal co-administration of calcium channel blockers with morphine or clonidine at the spinal level

Abstract.

Opioids, α₂-adrenoceptor agonists and blockers of voltage-gated calcium channels have been attributed antinociceptive activity, but only few studies have investigated their influence on the haemodynamic parameters. This study was performed to examine the changes in the mean arterial blood pressure (MAP) after intrathecal (i.t.) co-administration of morphine or clonidine with drugs blocking L- or N-type voltage gated calcium channels (verapamil and ω-conotoxin MVIIA, respectively) in anaesthetized rats.

Lower doses of clonidine (0.01–5 µg i.t.) produced dose-dependent decreases in MAP, while the highest dose of clonidine (20 µg i.t.) produced a pressor response. The administration of morphine (0.01–20 µg i.t.) caused only minor decreases of blood pressure and these appeared not to be dose dependent. Both ω-conotoxin MVIIA (1 ng–10 µg i.t.) and verapamil (1–100 µg i.t.) at higher doses decreased blood pressure significantly. ω-Conotoxin MVIIA caused a sustained decrease in MAP, while the effect of verapamil was short-lasting. Co-administration of morphine with verapamil or ω-conotoxin MVIIA led to dose-dependent and sustained decreases in blood pressure. The co-administration of ω-conotoxin MVIIA with clonidine did not influence the effect of clonidine significantly. In contrast, the combination of higher doses of verapamil with clonidine caused far greater blood pressure decreases than saline, verapamil or clonidine treatments alone.

These data suggest that the calcium channel blockers differentially influence the cardiovascular effect of the well-known antinociceptive drugs morphine and clonidine after intrathecal co-administration.