BEHAVIORAL-EFFECTS OF THE SYSTEMICALLY ACTIVE DELTA-OPIOID AGONIST BW373U86 IN RHESUS-MONKEYS

The behavioral effects of (+/-)-4-((alpha R)-alpha-((2S*,5R*)-4-allyl -2,5 piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide dihydrochlorid e (BW373U86), a nonpeptidic, systemically active, delta opioid agonist , were examined in rhesus monkeys. BW373U86, the mu agonist alfentanil and the kappa agonist U69,593 {(5 alpha,7 alpha,8 idinyl)-1-oxaspiro- (4,5)dec-8-yl)benzeneacetamide} all produced a dose-dependent suppress ion of response rates maintained under a fixed ratio 30 schedule of fo od presentation. The rate-suppressing effects of BW373U86 lasted 1 to 2 hr and were no longer apparent after 4 hr. The selective delta antag onist naltrindole (NTI) antagonized the effects of BW373U86 with relat ively high potency (pK(B) = 6.5) and the antagonist effects of NTI aga inst BW373U86 lasted approximately 4 hr. NTI was less potent in antago nizing alfentanil (pK(B) = 5.1) and the highest dose of NTI examined ( 10.0 mg/kg) did not antagonize U69,593. BW373U86 did not generalize to the discriminative stimulus effects of the mu agonist alfentanil or t he kappa agonist ethylketocyclazacine. BW373U86 also did not produce a ntinociceptive effects in the warm-water tail-withdrawal procedure, si gnificant respiratory depressant effects in monkeys breathing either a ir or 5% CO2 or reinforcing effects in a self-administration procedure . The highest dose of BW373U86 examined (1.78 mg/kg) produced convulsi ons in one monkey. The high relative potency of NTI to antagonize the rate-suppressing effects of BW373U86 was consistent with the character ization of BW373U86 as a systemically active, delta-selective agonist in rhesus monkeys. Under the conditions evaluated in the present study , the delta receptors to which BW373U86 binds do not appear to mediate antinociceptive, respiratory depressant or reinforcing effects in mon keys.