Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study represents the initial step in assessing the discriminative effects of spiradoline (U62,066), a potent congener of the selective kappa-opioid agonist, U50,488. Separate groups of rats were trained to discriminate between SC injections of saline and either 3.0 mg/kg spiradoline or 3.0 mg/kg morphine in a discrete-trial shock-avoidance/escape procedure. Spiradoline-trained rats generalized completely to U50,488 (ED50S for spiradoline and U50,488 were 0.66 and 8.71 mg/kg, respectively), but selected the choice lever appropriate for saline in generalization tests with graded doses of morphine, phencyclidine, and agonist-antagonist opioids with varying degrees of kappa activity, ethylketocyclazocine, nalorphine, and butorphanol. Morphine-trained rats did not generalize to spiradoline. Naltrexone (0.01 or 0.1 mg/kg) blocked surmountably the discriminative effects of both spiradoline and morphine, but was approximately 10-fold less potent against spiradoline. These results indicate that the discriminative effects of spiradoline are mediated by kappa-opioid receptors; meaningful mu-opioid and PCP/sigma components of action were not in evidence. The potency and apparent pharmacological selectivity of spiradoline suggest the potential value of this drug for studying kappa-opioid-mediated stimulus control of behavior.
 ...
PMID:Discriminative stimulus effects of spiradoline, a kappa-opioid agonist. 166 52

To assess the commonalities and differences in the discriminative stimulus properties of phencyclidine (PCP) and psychotomimetic opioids, rats were trained to discriminate PCP (2.0 mg/kg), cyclazocine (1.0 mg/kg), and saline in a three-choice discrete-trial avoidance paradigm. Stimulus control of behavior, defined as the reliable completion of 18 trials of a 20-trial session on the appropriate choice lever after administration of PCP, cyclazocine, or saline, was established in an average of 157 sessions. In tests of stimulus generalization, SKF-10,047 and dextrorphan engendered lever choices appropriate to both PCP and cyclazocine, sometimes in the same animal and at the same dose. The rats responded almost exclusively on the PCP-appropriate lever after ketamine and on the saline lever after morphine and d-amphetamine, indicating pharmacologic specificity. Naltrexone, in doses that had little effect on stimulus control of behavior by PCP, completely blocked cyclazocine-like stimulus control. Decreases in cyclazocine choices in the presence of naltrexone were associated with increases in PCP choices. These results support conclusions derived from two-choice procedures that psychotomimetic opioids have PCP-like stimulus effects, and provide direct evidence that these effects of cyclazocine are mediated by a component of action insensitive to an opiate antagonist.
 ...
PMID:Three-choice drug discrimination: phencyclidine-like stimulus effects of opioids. 640 61

The opioids SKF 10047, dl-cyclazocine, and dextrorphan have been shown to have phencyclidine (PCP)-like discriminative stimulus properties in the rat. In order to extend the generality of this observation, the stimulus effect of these and other opioids were evaluated in squirrel monkeys trained to discriminate between IM injections of saline and 0.25 mg/kg of PCP in a two-choice discrete-trial avoidance paradigm. Stimulus control of behavior was characterized by the reliable completion of at least 22 trials of a 25-trial session on the appropriate choice lever after an injection of saline or PCP. In tests of stimulus generalization, SKF 10047, d-cyclazocine, dextrorphan, normetazocine, dl-cyclazocine, l-cyclazocine, and dextromethorphan occasioned dose-related increases in PCP-appropriate responding. The first four of these compounds and, under some conditions, l- and dl-cyclazocine, produced stimulus control of behavior comparable to that produced by the PCP training dose. Six other opioids occasioned responding only on the saline-appropriate liver: ethylketocyclazocine. Ketocyclazocine, levorphanol, levallorphan, pentazocine, naltrexone. Naltrexone (1.0 or 4.0 mg/kg) attenuated slightly the PCP-like stimulus effects of SKF 10047 and dextrorphan, but increased PCP-appropriate responding with l- and dl-cyclazocine and levorphanol by enabling higher doses of these drugs to be tested without disruption of responding. The PCP-like stimulus effects of certain opioids appear to be mediated at neuronal substrates acted upon by PCP rather than at sites typically associated with opiate activity. These neuronal sites of action common to opioids and PCP may correspond to the sigma "opiate" receptor.
 ...
PMID:Phencyclidine-like discriminative stimulus properties of opioids in the squirrel monkey. 681 89

In rats trained to discriminate 0.04 mg/kg fentanyl from saline, phencyclidine (PCP) and the PCP-type drugs ketamine and (+/- )-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imine produced effects that are usually referred to as partial generalization. Partial generalization could conceivably result from low efficacy actions at the receptor mediating the discriminative stimulus effects of the training drug. The PCP-type drugs produced maximum percentages of drug lever (DL) selection intermediate between those produced by the training conditions, but their curves relating dose to percentage of DL selection were not shallower than that of fentanyl. The PCP-type drugs decreased DL selection produced by the training dose of fentanyl, but there was no relationship between these antagonist effects and the DL selection produced by the PCP-type drugs when given alone. Naltrexone antagonized DL selection produced by fentanyl, but not that produced by the PCP-type drugs. The potency order of the PCP-type drugs to produce DL selection was in agreement with their relative affinities for PCP receptors, but not with those for morphine receptors. The intermediate levels of DL selection produced by the PCP-type drugs were associated with increased lever selection latencies and increased responding on the nonselected lever; this pattern of effects resembled the behavior of animals that had not yet acquired the discrimination. The results suggest that PCP-type drugs produce intermediate levels of drug-appropriate responding in fentanyl-trained rats through mechanisms involving not opioid receptors and partial generalization, but involving PCP receptors and performance deficits conceivably resulting from state dependency. Thus, the results stress the importance of a pharmacological and behavioral analysis of intermediate responding in drug discrimination to examine its validity as a measure of efficacy and of stimulus similarity.
 ...
PMID:Effects of phencyclidine-type drugs in rats discriminating fentanyl from saline: pharmacological and behavioral characterization of intermediate levels of drug lever selection. 843 23