Pigeons were trained to discriminate between dextrorphan (10 mg/kg) and saline in a task in which 20 consecutive key pecks on either the left or right key, depending on whether dextrorphan or saline had been administered, produced food. During sessions in which stimulus generalization to other drugs was evaluated, 20 consecutive responses on either the dextrorphan- or saline-appropriate key produced food. Dextromethorphan and dexoxadrol produced dose-related stimulus control of behavior similar to that produced by dextrorphan. In contrast, the l-isomers of these compounds, levomethorphan, levoxadrol and levorphanol, at doses up to and including those that markedly decreased the rate of responding, produced responding primarily on the saline-appropriate key. In addition, both the d- and l-isomers of methadone, codeine, morphine, butorphanol and profadol resulted in predominantly saline-appropriate responding. l-Cyclorphan, dl-, l- and d-SKF-10,047 and l- and d-cyclazocine produced dose-related dextrorphan-appropriate responding, whereas l-oxilorphan (the 14-hydroxymorphinan analog of cyclorphan), dl-, l- and d-pentazocine, l- and d-ethylketazocine and l-naltrexone resulted in either responding exclusively on the saline-appropriate key or responding that was intermediate between that appropriate for saline and dextrorphan. Although levorphanol alone produced little or no dextrorphan-appropriate responding, the coadministration of naltrexone (1.0 mg/kg) and high doses of levorphanol, but not levoxadrol, resulted in responding similar to that produced by dextrorphan. The discriminative effects of dextrorphan, however, were unaffected by naltrexone. These results suggest that the discriminative effects of dextrorphan may be useful for characterizing opioid activity quite different from that produced by morphine-like compounds. The discriminative effects of dextrorphan are pharmacologically and structurally specific, stereo-selective and not antagonized by naltrexone. Moreover, it would appear that important differences exist among certain pairs of opioid stereoisomers; the actions of an opioid dextro-isomer are not simply predicted by the effects of the levo-isomer.
|Original language||English (US)|
|Number of pages||9|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1983|
ASJC Scopus subject areas
- Molecular Medicine