Pharmacological analysis of alpha(2)-adrenoceptor subtypes mediating analgesic, anti-inflammatory and gastroprotective actions.

Our previous findings suggest that alpha(2)-adrenoceptor stimulants induce gastroprotective action, the effect is likely to be mediated by alpha(2B)-adrenoceptor subtype. Clonidine (0.094 micromol/kg p.o.) and rilmenidine (0.014 micromol/kg p.o.) in gastroprotective dose range, as well as ST-91 (2.2 micromol/kg p.o.), a clonidine analogue showing higher affinity to alpha(2B)-adrenoceptor subtype than to alpha(2A)-one, inhibited the carrageenan-induced hyperalgesia in Randall-Selitto test, the antinociceptive action was reversed by yohimbine (5 micromol/kg s.c.) and the alpha(2B)-adrenoceptor antagonist prazosin (0.24 micromol/kg i.p.). Similarly, clonidine and rilmenidine in the same dose range reduced the oedema formation induced by carrageenan, yohimbine and the alpha(2A)-adrenoceptor antagonist BRL-44408 (3 micromol/kg i.p.) inhibited the anti-inflammatory effect; however, prazosin failed to affect it. These results suggest that alpha(2B/C)-like adrenoceptor subtype may be involved in the antihyperalgesic action, but not in the antiphlogistic effect of alpha(2)-adrenoceptor stimulants. The later effect may be mediated by alpha(2A)-like adrenoceptor subtype.