Pharmacological analysis of α2-adrenoceptor subtypes mediating analgesic, anti-inflammatory and gastroprotective actions

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