5-fluoronicotine, noranhydroecgonine, and pyridyl-methylpyrrolidine release acetylcholine and biogenic amines in rat cortex in vivo.
The effects of nicotinic receptor agonists 5-fluoronicotine, noranhydroecgonine and pyridyl-methylpyrrolidine on the cortical release of acetylcholine (ACh), norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were investigated with microdialysis in rat. 5-Fluoronicotine significantly elevated ACh to 76% above basal values and DA to 69% above baseline. Pyridyl-methylpyrrolidine significantly increased the release of ACh to 39% above basal values and NE to 63% above baseline. Noranhydroecgonine significantly elevated NE to 64% above basal values and DA to 147% above baseline. 5-Fluoronicotine did not affect NE release; pyridylmethylpyrrolidine did not alter DA release; and noranhydroecgonine did not significantly elevate ACh release. None of these agonists increased the release of 5-HT. All responses were blocked by prior administration of mecamylamine, a nicotinic receptor antagonist. The distinctive neurotransmitter-related profiles for the three agonists are suggestive of activity at subtypes of nicotinic receptors, an effect that may be related to the structural diversity of these compounds.
Summers
K L
KL
Dept. Pharmacology, Southern Illinois University School of Medicine, Springfield 62794-1222, USA.
Lippiello
P
P
Verhulst
S
S
Giacobini
E
E
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009538:Nicotine / Q000031:analogs & derivatives / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D001679:Biogenic Amines; D018722:Nicotinic Agonists; D011725:Pyridines; D011759:Pyrrolidines; C097950:noranhydroecgonine; C097951:5-fluoronicotine; C069076:N-(3-pyridylmethyl)pyrrolidine; D009538:Nicotine; D003042:Cocaine; D000109:Acetylcholine