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-precip3tated withdrawal jumping in the morphine-dependent mice. Cross tolerance to the antinociceptive action induced by tizanidine and clonidine was developed. These results suggest that α2-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.
All Science Journal Classification (ASJC) codes
- Clinical Biochemistry
- Biological Psychiatry
- Behavioral Neuroscience