5-Fluoronicotine,noranhydroecgonine, and pyridyl-methylpyrrolidine release acetylcholine and biogenic amines in rat cortex in vivo |
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Authors: | Kathleen L Summers Patrick Lippiello Steven Verhulst Ezio Giacobini |
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Institution: | (1) Dept. Pharmacology, Southern Illinois University School of Medicine, P.O. Box 19230, 62794-1222 Springfield, Illinois;(2) Dept. Statistics, Southern Illinois University School of Medicine, P.O. Box 19230, 62794-1222 Springfield, Illinois;(3) Research and Development Department, R.J. Reynolds Tobacco Company, 27102 Winston-Salem, North Carolina |
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Abstract: | 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. |
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Keywords: | Cortex 5-fluoronicotine microdialysis neurotransmitters nicotine noranhydroecgonine pyridyl-methylpyrrolidine |
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