(-)6-n-Propylnicotine antagonizes the antinociceptive effects of (-)nicotine.
Several 6-alkyl analogues of nicotine were examined in radioligand binding and in vivo functional assays. Although (-)6-ethylnicotine (3) binds with high affinity at nACh receptors (Ki=5.6 nM) and produces nicotine-like actions, its n-propyl homologue (-)4 (Ki=22 nM) failed to produce such effects. In fact, (-)4 antagonized the antinociceptive effects of (-)nicotine in the tail-flick assay in mice, but not the spontaneous activity or discriminative stimulus effects of (-)nicotine. Compound (-)4 appears to selectively antagonize only one of the three effects examined and is an interesting cholinergic agent for subsequent investigation.
Dukat
Malgorzata
M
Department of Medicinal Chemistry, School of Pharmacy, Box 980540, Virginia Commonwealth University, Richmond, VA 23298-0540, USA.
El-Zahabi
Mohamed
M
Ferretti
Giovanni
G
Damaj
M Imad
MI
Martin
Billy R
BR
Young
Richard
R
Glennon
Richard A
RA
D000700:Analgesics / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D004192:Discrimination, Psychological / Q000187:drug effects; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity; D009538:Nicotine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis* / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D011869:Radioligand Assay; D011978:Receptors, Nicotinic / Q000378:metabolism; D013329:Structure-Activity Relationship
C471911:6-n-propylnicotine; D000700:Analgesics; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine