ANTINOCICEPTIVE ACTION OF DBO-17 AND DBO-11 IN MICE - 2 3,8-DIAZABICYCLO(3.2.1.)OCTANE DERIVATES WITH SELECTIVE MU-OPIOID RECEPTOR AFFINITY

Two 3,8 diazabicyclo (3.2.1.) octane derivates, namely DBO 17 and DBO 11, were studied for the opioidlike activity. In the rat brain membran e preparation binding studies, DBO 17 and DBO 11 showed a high affinit y and selectivity for the mu opioid receptor (K-i's: 5.1 and 25 nM, re spectively). DBO 17 and DBO 11 inhibited the nociceptive response in t he hot-plate test of mice with ED50 values of 0.16 mg/kg and 0.44 mg/k g, respectively. The antinociceptive action of both DBO 17 and DBO 11 was blocked by naloxone. Tolerance to the antinociceptive ac tion of D BO 17 and DBO 11 was present after 13 and 7 days of repeated treatment , respectively. Both DBO 17 and DBO 11 were ineffective in morphine-to lerant mice and vice versa. Chronic treatments (three times daily for seven consecutive days) of DBO 17 and DBO 11 induced a naloxone-precip itated withdrawal syndrome in DBO 17 treated mice similar to that in m orphine treated mice, whereas in DBO 11 treated mice abstinence signs were virtually absent. These results indicate an interesting pharmacol ogical profile that suggests these compounds as possible new candidate s for the clinical treatment of pain.