Dissociation of the motor effects of (+)-pentazocine from binding to sigma 1 sites.
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.
Matsumoto
R R
RR
Department of Neurology, University of California Irvine 92717, USA.
Bowen
W D
WD
Walker
J M
JM
Patrick
S L
SL
Zambon
A C
AC
Vo
V N
VN
Truong
D D
DD
De Costa
B R
BR
Rice
K C
KC
D000375:Aging / Q000378:metabolism; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004421:Dystonia / Q000139:chemically induced / Q000523:psychology; D006220:Haloperidol / Q000494:pharmacology; D019416:Head Movements / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009068:Movement / Q000187:drug effects*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010423:Pentazocine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000502:physiology*; D012012:Red Nucleus / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D002492:Central Nervous System Depressants; D009292:Narcotic Antagonists; D009294:Narcotics; D017480:Receptors, sigma; D006220:Haloperidol; D010423:Pentazocine