Nicotinates activity

Corrigall, W.A., Coen, K.M., Adamson, K.L. Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area. Brain Res. 653 278, 1994. 

Pidoplichko, V.I., DeBiasi, M., Williams, J.T., Dani, J.A. Nicotine activates and desensitizes midbrain dopamine neurons. Nature. 390 401, 1997. 

Tapper, A.R., McKinney, S.L., Nashmi, R. et al. Nicotine activation of alpha4 receptors sufficient for reward, tolerance, and sensitization. Science. 306 1029, 2004. 

The range of nicotinic acid activity in blood, for a group of 28 normal subjects is 3.9-9.6 qg/ml. Only a fraction of less than 1% (0.016-0.05 pg/ml) of this quantity was present in serum. The range in urine was 1.16-1.54 pg/ml. Ninety-seven to 101% of added combinations of nicotinic acid and nicotinamide was recovered when added to blood and urine. In blood, appreciable nicotinic activity is observed only after... 

Cerebral blood flow and glucose metabolism Nicotine increases cerebral blood flow (Hara et al. 1993 Yokoi et al. 1993). Functional MRI of smokers who were administered intravenous nicotine shows increases of cerebral blood flow in several areas of the brain. Corresponding to feelings of mood elevation, nicotine activates the nucleus accumbens, amygdala, cingulate cortex, and frontal lobes. This activation is very consistent with functional systems subserving arousal and reinforcement. 

Lewis R, Wake G, Court G, Court JA, Pickering AT, Kim YC, Perry EK. (1994). Non-ginsenoside nicotinic activity in ginseng species. Phytother Res. 13(1) 59-64. 

Pich EM, Paghusi SR, Tessari M, Talabot-Ayer D, Hooft v H, Chiamulera C (1997) Common neural substrates for the addictive properties of nicotine and cocaine. Science 275 83-86 PidopUchko VI, DeBiasi M, Williams JT, Dani JA (1997) Nicotine Activates and Desensitizes Midbrain Dopamine Neurons. Nature 390 401 04 PietUa K, Ahtee L (2000) Chronic nicotine administration in the drinking water affects the striatal dopamine in mice. Pharmacol Biochem Behav 66 95-103 Puttfarcken PS, Jacobs I, Faltynek CR (2000) Characterization of nicotinic acetylcholine receptor-mediated [ H]-dopamine release from rat cortex and striatum. Neuropharmacology 39 2673-2680... 

Pidoplichko V, De Biasi M, Williams JT, Dani J (1997) Nicotine activates and desensitizes midbrain dopamine neurones. Nature 390 401 04... 

Acetylcholine [a se teel KOE leen] is a quarternary ammonium compound that cannot penetrate membranes. Although it is the neurotransmitter of parasympathetic and cholinergic nerves, it is therapeutically of no importance because of its multiplicity of actions and its rapid inactivation by acetylcholinesterase. Acetylcholine has both muscarinic and nicotinic activity. Its actions include ... 

Coned answer = B. Nicotine activates the sympathetic nervous system and causes hypertension and tachycardia. 

Repeated exposure, as occurs in habitual smokers, leads to an increased rate of metabolism of nicotine and decreased sensitivity of the receptors to the nicotine. More nicotine is therefore required to satisfy the needed stimulation, and tolerance develops. This is a separate effect from addiction which seems to be due to increased levels of a substance called dopamine in the brain. This is due to the nicotine activating nerve cells which results in increased release of dopamine and causes a reduction in the amount of an enzyme that destroys dopamine. It seems that other addictive drugs may also work by increasing dopamine levels. 

Shortening or lengthening the chain of atoms that separates the e.ster group from the onium moiety reduces mu.s-carinic activity. An a substitution on the choline moiety decreases both nicotinic and muscarinic activity, but muscarinic activity is decreased to a greater extent. Nicotinic activity is decreased to a greater degree by substitution on the... 

Bethanechol Chloride, USP. Bethanechol. jS-mcthyl-choline chloride carbamate. (2-hydroxypropyl)trimethylam-monium chloride carbamate, carbamylmelhylcholinc chloride (Urecholinc), is nonspecific in its action on muscarinic receptor. subtypes but appears to be more effective at eliciting pharmacological action of M> receptors. It has pharmacological properties similar to those of methacholinc. Both are esters of nicthylcholine and have feeble nicotinic activity. Bethanechol is inactivated more slowly by AChE in vivo than is mcthacholine. It is a carbamyl ester and is expected to have stability in aqueous solutions similar to that of carbachol. 

Imidacloprid is a neonicotinoid insecticide that is registered for many uses, including grub and termite control, crop protection, and to control fleas and ticks on companion animals. Its insecticidal activity is attributed to nicotinic activity on post-synaptic receptors. 

It was concluded that the nicotinic activity of choline phenyl ether and of choline o-tolyl ether is a reflection of the ability of the molecule to assume a "planar" conformation when interacting with the ganglionic nicotinic receptor. In contrast, the inactive 2,6-xylyl ether of choline cannot assume this planar disposition. Evaluation of additional conformation-ally restricted aiyl choline ethers (44-47) revealed that only the piperidine derivative (47) is a ganglionic stimulant (98). 

Some aromatic ethers of choline display marked nicotinic activity, but they are inactive at muscarinic sites (94). The o-tolyl ether of choline is a potent ganglionic stimulant (95), but the 2,6-xylyl ether of choline is inert as a nicotinic agent (96). 

Muscarinic activities are tested on the guinea pig longitudinal ileal muscle in all cases except acetyl-p-methylcholine, vdiidi is tested on the circular muscle from fundus cf rabbit stomach. Nicotinic activities are tested on the frog rectus abdominis muscle. 

One other very useful result was obtained from methacholine. It was discovered that the introduction of the methyl group led to significant muscarinic activity and very little nicotinic activity. Therefore, methacholine showed a good selective action for the muscarinic receptor. This result is perhaps more important than the gain in stability. 

In addition, it has been shown recently that bupropion is a potent inhibitor of central nAChRs and that it blocks nicotine activation of these receptors in a dose-dependent noncompetitive fashion (208). This suggests that the nicotinic antagonist effect contributes to bupropion mechanism of action in smoking cessation. 

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