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Abstract

Substitution and antagonism in rats trained to discriminate (+)-N-allylnormetazocine from saline.

R L Balster
Journal of Pharmacology and Experimental Therapeutics June 1989, 249 (3) 749-756;
R L Balster
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Abstract

(+)-N-Allylnormetazocine (NANM) binds to at least two sites in the mammalian central nervous system, a high-affinity, haloperidol-sensitive site and a lower-affinity site identified as the phencyclidine (PCP) receptor. The relevance of these sites to the discriminative stimulus properties of (+)-NANM was evaluated in rats trained to discriminate (+)-NANM from saline. Drugs with a high affinity for the haloperidol-sensitive site, including haloperidol, (+)-ketocyclazocine, 1,3-di-ortho-tolyl-guanidine and (-)-butaclamol failed to substitute for the (+)-NANM stimulus. In addition, when they were tested in combination with (+)-NANM, only haloperidol evidenced any antagonistic effects. The antagonistic effects of haloperidol were incomplete and only occurred at doses that substantially disrupted responding. Evidence obtained earlier that (+)-3-(3-hydroxyphenyl)-N-(1-propyl) piperidine could antagonize (+)-NANM was not replicated. On the other hand, PCP-like drugs from diverse chemical classes, including PCP, ketamine, MK-801, (-)-2-methyl-3,3-diphenyl-3-propanolamine, etoxadrol and dextrorphan, all substituted fully for the (+)-NANM stimulus with a potency predicted by their relative potency for PCP-like discriminative stimulus effects and relative affinity for the PCP receptor. Taken together, these results fail to provide evidence for an important role for the high-affinity haloperidol-sensitive binding site for (+)-NANM in its discriminative stimulus properties. Instead, activity at the PCP receptor is predictive of (+)-NANM-like effects.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 249, Issue 3
1 Jun 1989
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Abstract

Substitution and antagonism in rats trained to discriminate (+)-N-allylnormetazocine from saline.

R L Balster
Journal of Pharmacology and Experimental Therapeutics June 1, 1989, 249 (3) 749-756;

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Abstract

Substitution and antagonism in rats trained to discriminate (+)-N-allylnormetazocine from saline.

R L Balster
Journal of Pharmacology and Experimental Therapeutics June 1, 1989, 249 (3) 749-756;
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