Chronic spinal infusion of dexmedetomidine, ST-91 and clonidine: spinal alpha 2 adrenoceptor subtypes and intrinsic activity

The antinociceptive effect (hot plate test) and behavioral changes produced by the continuous 7-day i.t. infusion of alpha 2 adrenoceptor agonists dexmedetomidine (10 and 3 nmol/hr), clonidine (100 and 30 nmol/hr) and 2-(2,6-diethylphenylamino)-2-imidazoline (ST-91) (30 and 10 nmol/hr) were examined in rats. The highest doses of each agonist produced an equivalent increase in hot plate latency on day 1 of infusion. These effects diminished to near base line by 5 to 7 days. In separate groups, i.t. dose-response curves were obtained with dexmedetomidine, clonidine and ST-91 in groups of rats which had received a 7-day infusion of saline or the equianalgesic concentrations of dexmedetomidine (10 nmol/hr) or ST-91 (30 nmol/hr). Dose-response curves in drug-infused animals showed a right shift as compared to the vehicle-infused rats. Calculation of the ratio of the ED50 values (tolerance ratio: drug vs. control) in animals receiving the continuous infusion of dexmedetomidine vs. saline indicated: 8- (6-12), 36- (19-54) and 1.0- (0.6-1.5) (ratio with 95% Cl) fold rightward shifts of dexmedetomidine, clonidine and ST-91 dose-response curves, respectively. Chronic infusion of ST-91 resulted in 62- (36-127), 22- (13-46) and 0.9- (0.7-1.1) fold rightward shift of the ST-91, clonidine and dexmedetomidine dose-response curves, respectively. Previously, we have shown that dexmedetomidine and clonidine act upon spinal alpha 2 adrenoceptor, which appeared distinguishable from that acted upon by ST-91.(ABSTRACT TRUNCATED AT 250 WORDS)