Comparison of tizanidine and morphine with regard to tolerance-developing ability to antinociceptive action.
The antinociceptive, tolerance-developing and anti-withdrawal activities of tizanidine [5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzo-thiadiazole] were investigated by comparing its effects with those of morphine and clonidine in tail-flick-, hot plate-, acetic acid-induced writhing-, and naloxone-precipitated withdrawal jumping-tests. The antinociceptive action of tizanidine was not altered by naloxone, while that of morphine was antagonized. Tolerance to the tizanidine-induced antinociceptive action and to motor incoordination was developed by successive administration of tizanidine. In the tizanidine-tolerant mice, the antinociceptive action of morphine was significantly decreased, but not sleeping time induced by pentobarbital. The action of tizanidine was not modified in the morphine-tolerant mice. Tizanidine failed to induce morphine-withdrawal jumping and to inhibit naloxone-precipitated withdrawal jumping in the morphine-dependent mice. Cross tolerance to the antinociceptive action induced by tizanidine and clonidine was developed. These results suggest that alpha 2-adrenoreceptors may be involved in the action mechanism of tizanidine, but not opioid receptors. Functional tolerance to tizanidine action may be developed by successive administration of tizanidine.
D000700:Analgesics; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009048:Motor Skills / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D010147:Pain Measurement; D012890:Sleep / Q000187:drug effects
D000700:Analgesics; D009270:Naloxone; C023754:tizanidine; D009020:Morphine; D003000:Clonidine