PT - JOURNAL ARTICLE AU - M H Ossipov AU - S Harris AU - P Lloyd AU - E Messineo TI - An isobolographic analysis of the antinociceptive effect of systemically and intrathecally administered combinations of clonidine and opiates. DP - 1990 Dec 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1107--1116 VI - 255 IP - 3 4099 - http://jpet.aspetjournals.org/content/255/3/1107.short 4100 - http://jpet.aspetjournals.org/content/255/3/1107.full SO - J Pharmacol Exp Ther1990 Dec 01; 255 AB - The antinociceptive interaction of opiate analgesics with clonidine was examined with the tail-flick and 55 degrees C hot plate tests. Male Sprague-Dawley rats received fixed ratios of clonidine to fentanyl, meperidine or morphine by i.v. and intrathecal injection. Data are expressed as percentage of maximal possible effect and the dose producing 50 percentage of maximal possible effect for each drug or drug combination is used to index potency. The rank order of potency in both tests after i.v. administration is fentanyl much greater than clonidine greater than meperidine greater than or equal to morphine and after intrathecal administration it is morphine greater than fentanyl much greater than clonidine much greater than meperidine. Isobolographic analysis shows that the effect of clonidine combined with an opiate is additive after i.v. administration; the exception is that morphine and clonidine are synergistic in the hot plate test. The intrathecal combinations of clonidine with morphine or meperidine produces a supra-additive antinociceptive effect in the tail-flick test but not in the hot plate test. Fentanyl does so in both tests. These data confirm a positive interaction between clonidine and opiates in producing antinociception. This interaction may be additive or synergistic, depending on route of administration and the nociceptive test used. The timing of injections and pharmacokinetic factors may also influence the results. Moreover, these results suggest that the interaction between the opiate and alpha-2 adrenergic receptors occurs within the spinal cord.