A comparison of (-)-deoxybenzomorphans devoid of opiate activity with their dextrorotatory phenolic counterparts suggests role of sigma 2 receptors in motor function.
Three novel benzomorphans, (+)-N-benzylnormetazocine, (-)-deoxy-N-benzylnormetazocine, and (-)-deoxypentazocine were tested for their ability to produce circling behavior in rats following intranigral microinjections. Dose studies revealed the following rank order of potency: (-)-deoxypentazocine > (-)-deoxy-N-benzylnormetazocine > (+)-N-benzylnormetazocine. This rank order approximates that for affinities for sigma 2 receptors but not sigma 1 receptors. It is very unlikely that the effects of the (-)-deoxybenzomorphans were mediated by opiate receptors for the following reasons: (1) consistent with the known requirement for the phenolic hydroxyl group for opiate activity, both (-)-deoxy compounds showed very low affinity for opiate receptors; (2) naloxone (4 micrograms) co-administered with (-)-deoxy-N-benzylnormetazocine failed to reduce its efficacy; (3) both (-)-deoxy compounds failed to produce marked analgesic effects in the tail flick test following systemic injections of 20 mg/kg s.c. These finding suggest that sigma 2 receptors mediate the motor effects of sigma ligands in rats.
Schrier Research Laboratory, Department of Psychology, Brown University, Providence, RI 02912.
J M
JM
Walker
W D
WD
Bowen
S L
SL
Patrick
W E
WE
Williams
S W
SW
Mascarella
X
X
Bai
F I
FI
Carroll
D000818:Animals; D001575:Benzomorphans / Q000378:metabolism / Q000494:pharmacology*; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000737:chemistry; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000737:chemistry*; D010146:Pain / Q000503:physiopathology; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism; D017480:Receptors, sigma / Q000378:metabolism / Q000502:physiology*; D012399:Rotation; D013237:Stereoisomerism
D001575:Benzomorphans; D009294:Narcotics; D010636:Phenols; D011957:Receptors, Opioid; D017480:Receptors, sigma; C014716:normetazocine; D009270:Naloxone; D003496:Cyclazocine