PT  - JOURNAL ARTICLE
AU  - Picker, M J
TI  - Kappa agonist and antagonist properties of mixed action opioids in a pigeon drug discrimination procedure.
DP  - 1994 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1190--1198
VI  - 268
IP  - 3
4099  - http://jpet.aspetjournals.org/content/268/3/1190.short
4100  - http://jpet.aspetjournals.org/content/268/3/1190.full
SO  - J Pharmacol Exp Ther1994 Mar 01; 268
AB  - Previous investigations indicate that mixed action opioids (i.e., opioids with activity at a combination of opioid receptor sites or a combination of opioid and nonopioid sites) often possess kappa-like stimulus effects in the rat and monkey, but mu-like stimulus effects in pigeons. In the present investigation, the kappa agonist and antagonist actions of a series of mixed action opioids were examined in pigeons trained to discriminate a 0.017-mg/kg dose of the kappa agonist bremazocine from saline. The mixed-action opioids (-)-n-allylnormetazocine, (-)-cyclazocine, (-)-metazocine, levallorphan, buprenorphine, nalbuphine, butorphanol and nalorphine failed to substitute for the bremazocine stimulus. When administered in combination with the training dose of bremazocine, each of these opioids produced a dose-related antagonism of the bremazocine stimulus. With the exceptions of butorphanol and (-)-metazocine, the antagonist effects of these opioids were surmountable. Buprenorphine, (-)-n-allylnormetazocine and levallorphan produced their kappa antagonist effects at doses approximately 2 to 3 log units lower than those that decreased rates of responding when these opioids were administered alone, whereas approximately 1 log unit separated the kappa antagonist and rate-decreasing effects of nalorphine, nalbuphine and (-)-cyclazocine. In contrast, the kappa antagonist effects of butorphanol and (-)-metazocine were observed only at doses of markedly decreased response rates. A somewhat different profile was obtained with ethylketocyclazocine and ketocyclazocine in that these mixed action opioids produced partial substitution for and partial antagonism of the bremazocine stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)