Dissociation of the motor effects of (+)-pentazocine from binding to sigma 1 sites

Eur J Pharmacol. 1996 Apr 22;301(1-3):31-40. doi: 10.1016/0014-2999(96)00008-8.

Abstract

Radioligand binding and behavioral studies were conducted to determine whether a relationship existed between the motor effects produced by (+)-pentazocine and its binding to sigma sites. Scatchard analyses revealed decreased [3H](+)-pentazocine binding in middle aged rats (5-6 months old) compared to young adult rats (2-3 months old). However, there was no difference between the extent of circling behavior or dystonia produced by microinjection of (+)-pentazocine into the substantia nigra or red nucleus in the older animals compared to the young adult rats. There was also a significant decrease in [3H](+)-pentazocine binding in rats chronically treated with haloperidol. Again, however, despite the reduction in [3H](+)-pentazocine binding, there was no difference between the extent of dystonia produced by unilateral intrarubral microinjection of (+)-pentazocine into animals chronically treated with haloperidol vs. saline. The postural changes produced by (+)-pentazocine could not be attenuated with coadministration of the putative sigma receptor antagonist BD1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino) ethylamine), or the opiate receptor antagonist naloxone. However, the (+)-opiate, (+)-nordihydrocodeinone, partially attenuated the postural effects of (+)-pentazocine, despite its very low affinity for sigma 1, sigma 2, or opiate receptors. Taken together with previous studies, the results suggest that [3H](+)-pentazocine is a potent and selective probe for sigma 1 binding sites, but the in vivo effects of (+)-pentazocine cannot be fully attributed to actions through these sites. Some of the in vivo effects of (+)-pentazocine appear to involve other binding sites that are not detected under the conditions normally used in in vitro assays.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / metabolism
  • Animals
  • Central Nervous System Depressants / pharmacology
  • Dystonia / chemically induced
  • Dystonia / psychology
  • Haloperidol / pharmacology
  • Head Movements / drug effects
  • In Vitro Techniques
  • Male
  • Membranes / drug effects
  • Membranes / metabolism
  • Movement / drug effects*
  • Narcotic Antagonists / pharmacology
  • Narcotics / pharmacokinetics*
  • Narcotics / pharmacology*
  • Pentazocine / pharmacokinetics*
  • Pentazocine / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, sigma / antagonists & inhibitors
  • Receptors, sigma / physiology*
  • Red Nucleus / drug effects
  • Red Nucleus / metabolism
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism

Substances

  • Central Nervous System Depressants
  • Narcotic Antagonists
  • Narcotics
  • Receptors, sigma
  • Haloperidol
  • Pentazocine