Acetylcholine nicotinic activity

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... 

The alkaloids which influence acetylcholine esterase activity are eserine, galan-thamine, nicotine, lobeline and tubocurarine. All of these alkaloids are very active. 

No difference has been observed in the interactions of the two enantiomers of isoflurane with hpid bilayers. But the (5)-enantiomer of isoflurane is two times more active than the (7 )-enantiomer toward a calcium channel receptor, that is sensitive to volatile anesthetic agents, while nodifference in activity has been observed toward an anesthetic nonsensitive receptor. The (5)-enantiomer of isoflurane is also more active than the (R)-enantiomer toward acetylcholine nicotinic receptor and GABA receptor. These data strongly suggest that fluoroethers interact not only with cerebral membranous lipids but also with receptor proteins. 

The tobacco compound nicotine has been used as an insecticide for over 200 years. It is especially effective against sucking insects, such as aphids, and has excellent contact activity. Related compounds are neonicotinoids (e.g., imidacloprid), which have similar insecticidal activity, but are less toxic to mammals. Nicotine and imidacloprid mimic the action of acetylcholine, which is the major excitatory neurotransmitter in an insect s central nervous system. The action of acetylcholine is stopped by the enzyme acetylcholinesterase, which rapidly breaks down acetylcholine. Nicotine and imidacloprid are also neuroexcitatory, but do so persistendy, since they are not affected by acetylcholinesterase. Overstimulation of the nervous system often leads to convulsions, paralysis, and death. 

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 ... 

Bisbenzylisoquinolines (macrocyclic or linear, formed by 2 benzylisoquinolines) (+)-tubocurarine (macrocyclic) (acetylcholine (nicotinic) receptor antagonist and skeletal muscle relaxant major component of Chondrodendron species (Menispermaceae) pareira bark-derived curare arrow poison) dauricine (linear) (Menispermaceae curarelike anaesthetic) rodiasine (macrocyclic) (Ocotoea venenosa (Lauraceae) curare-like skeletal muscle relaxant) cepharanthine (macrocyclic) (Stephania species (Menispermaceae) anti-mycobacterial active against leprosy and tuberculosis). 

Myasthenia gravis is a disease of autoimmunity caused by the production of an antibody directed against the acetylcholine receptor in skeletal muscle. In this disease, B and T lymphocytes cooperate in producing a variety of antibodies against the nicotinic acetylcholine receptor. The antibodies then bind to various locations in the receptor and cross-link the receptors, forming a multireceptor antibody complex. The complex is endocytosed and incorporated into lyso-somes, where it is degraded. Mya Sthenia, therefore, has fewer functional receptors for acetylcholine to activate. 

Approximately 40-60 mg of nicotine (43) is a lethal dose for an adult human the LD50 i.v. in mouse is 0.3 mg/kg (Wink, 1993). This base is the main pharmacologically active component of tobacco smoke and probably is responsible for the addictive nature of cigarettes. The pharmacology of nicotine and other Nicotiana alkaloids has been reviewed (Fodor and Colasanti, 1985). Nicotine mimics acetylcholine and activates acetylcholine receptors (Wink, 1993). 

Homoanatoxin-a Neurotoxins Nicotinic acetylcholine receptor activator... 

Photolabile precursors of neurotransmitters ( caged neurotransmitters) that are biologically inactive have been developed. A photolabile precursor of carbamoylcholine, a stable analog of acetylcholine that activates the nicotinic acetylcholine receptor, is shown in the inset to Fig. 4. Photolabile precursors of all the major neuro-transmitters are now available. This photolabile precursor of carbamoylcholine ([A7-(a-carboxy-2-nitrobenzyl)-... 

Several cholinergic strategies, other than cholinesterase inhibition, have been employed with the intention of ameliora ting the symptoms of AD. These include precursor loading acetylcholine release enhancement, and direct activation of both muscarinic and nicotinic receptors. 

Acetylcholine. Acetylcholiae (ACh) (1) is a crystalliae material that is very soluble ia water and alcohol. ACh, synthesized by the enzyme choline acetyltransferase (3), iateracts with two main classes of receptor ia mammals muscarinic (mAChR), defiaed oa the basis of the agonist activity of the alkaloid muscarine (4), and nicotinic (nAChR), based on the agonist activity of nicotine (5) (Table 1). m AChRs are GPCRs (21) n AChRs are LGICs (22). 

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