Nicotinic effects receptors

Chapter 1 which showed that since muscarine mimicked some of the actions of ACh (but not all) while nicotine mimicked the other actions of ACh, then ACh probably acted on two distinct types of receptors. The fact that atropine antagonised the muscarinic effects of ACh but not the nicotinic effects, while tubocurarine blocked the nicotinic effects provided firm evidence for this concept. These simple qualitative observations by Langley and others at the beginning of the twentieth century led to the development of more quantitative pharmacological methods that were subsequently used to identify and classify receptors. These methods were based on the use of both (1) agonist and (2) antagonist drugs ... 

Nicotine increased DA levels both in vivo11,193 and in vitro. 94 196 Nicotine197 and its metabolites198 were found to both release and inhibit the reuptake of DA in rat brain slices, with uptake inhibition occurring at a lower concentration than that required for DA release. In addition, the (-) isomer was more potent than the (+) isomer.197 However, the effects of nicotine upon DA release and uptake were only apparent when brain slices were utilized because nicotine was unable to affect DA when a synaptosomal preparation was utilized.197 These results indicate that nicotine exerts its effects upon the DAT indirectly, most likely via nicotine acetylcholine receptors. This finding was supported by the results of Yamashita et al.199 in which the effect of nicotine on DA uptake was examined in PC 12 and COS cells transfected with rat DAT cDNA. Nicotine inhibited DA uptake in PC 12 cells that possess a nicotine acetylcholine receptor. This effect was blocked by the nicotinic antagonists hexamethonium and mecamylamine. Additionally, nicotine did not influence DA uptake in COS cells, which lack nicotinic acetylcholine receptors. 

Lukas, R. J. Effects of chronic nicotinic ligand exposure on functional activity of nicotinic acetylcholine receptors expressed by cells of the PC12 rat pheochromocytoma or the TE671/RD human clonal line. J. Neurochem. 56 1134, 1991. 

Marubio, L.M., Gardier, A.M., Durier, S. et al. Effects of nicotine in the dopaminergic system of mice lacking the alpha4 subunit of neuronal nicotinic acetylcholine receptors. Eur. J. Neurosci. 17 1329, 2003. 

Ke, L., Eisenhour, C., Bencherif, M., Lukas, R. Effects of chronic nicotine treatment on expression of diverse nicotinic acetylcholine receptor subtypes. I. Dose- and time-dependent effects of nicotine treatment. J. Pharmacol. Exp. Ther. 286 825, 1998. 

Ochoa, E., Chattopadhyay, A., McNamee, M. Desensitization of the nicotinic acetylcholine receptor Molecular mechanisms and effect of modulators. Cell Mol. Neurobiol. 9 141, 1989. 

Cosgrove, K., Ellis, S., Al-Tikriti, M. et al. Assessment of the effects of chronic nicotine on P2-nicotinic acetylcholine receptors in nonhuman primate using [I-123]5-IA-85830 and SPECT. Paper presented at the 66th Annual Scientific Meeting of the College on Problems of Drug Dependence, 2004, San Juan, Puerto Rico. 

An even simpler protocol for performing nucleophilic substitutions (aminations) and Suzuki reactions in one pot was reported by the Organ group for the generation of a 42-member library of styrene-based nicotinic acetylcholine receptor (nAChR) antagonists (Scheme 6.21) [49]. After considerable experimentation, the authors found that simultaneous nucleophilic displacement and Suzuki coupling could be carried out very effectively by charging the microwave process vessel with the palladium catalyst (0.5 mol% palladium-on-charcoal), the boronic acid [R1B(OH)2], the... 

Nicotine is the psychoactive ingredient of cigarettes and definitely accounts for the side effect quality of cigarette smoking. Nicotine mimics the neurotransmitter acetylcholine at one of the subclasses of the nicotinic acetylcholine receptors. Nicoti-... 

Nicotine, the principal psychoactive alkaloid in tobacco, has cognitive-enhancing effects. It directly activates nicotinic acetylcholine receptors in brain areas critical for cognition, creating both acute and chronic effects. 

Finally, a thorough receptor binding study by Raffa and colleagues (1998) showed that hypericin extracts had no effect at adrenergic (alpha or beta), adenosine, angiotensin, benzodiazepine, dopamine, bradykinin, neuropeptide Y, PCP, NMDA, opioid, cholecystokinin A, histamine HI, or nicotinic ACh receptors. Although comprehensive, this study did not look at the binding of any other hypericum constituents. 

Rao TS, Correa LD, Lloyd GK. (1997). Effects of lobeline and dimethyl-phenylpiperazinium iodide (DMPP) on N-methyl-D-aspartate (NMDA)-evoked acetylcholine release in vitro evidence for a lack of involvement of classical neuronal nicotinic acetylcholine receptors. Neuropharmacology. 36(1) 39-50. 

Reitstetter R, Lukas RJ, Gruener R. (1999). Dependence of nicotinic acetylcholine receptor recovery from desensitization on the duration of agonist exposure. J Pharmacol Exp Ther. 289(2) 656-60. Ribeiro EB, Bettiker RL, Bogdanov M, Wurtman RJ. (1993). Effects of systemic nicotine on serotonin release in rat brain. Brain Res. 621(2) 311-18. 

Stankov B, Cimino M, Marini P, Lucini V, Fraschini F, dementi F. (1993). Identification and functional significance of nicotinic choiinergic receptors in the rat pineal gland. NeuroscI Lett. 156(1-2) 131-34. Stein MA, Krasowski M, Leventhai BL, Phiiiips W, Bender BG. (1996). Behavioral and cognitive effects of methyixanthines. A meta-anaiysis of theophylline and caffeine. Arch Pedlatr Adolesc Med. 150(3) 284-8. 

Turchi J, Holley LA, Sarter M. (1995). Effects of nicotinic acetylcholine receptor ligands on behavioral vigilance in rats. Psychopharmacology (Berlin). 118(2) 195-205. 

Hogg RC, Raggenbass M, Bertrand D (2003) Nicotinic acetylcholine receptors from structure to brain function. Rev Physiol Biochem Pharmacol 147 1 6 Holmes S, Zwar N, Jimenez-Ruiz CA, Ryan PJ, Browning D, Bergmann L, Johnston JA (2004) Bupropion as an aid to smoking cessation a review of real-life effectiveness. Int J Chn Pract 58 285-291... 

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