Nicotine, target

Historically ganglionic nAChR have been targets for treating hypertension. The discovery of a large family of nAChR subtypes in the CNS, coupled with observations that nicotine has anti-nociceptive, neuro-protective and cognitive effects, has led to the recognition that neuronal nAChR are potential targets... 

Jensen AA, Frolund B, Liljefors T et al (2005) Neuronal nicotinic acetylcholine receptors structural revelations, target identifications, and therapeutic inspirations. J Med Chem 48 4705—4745... 

Another possible target for toxins are the receptors for neurotransmitters since such receptors are vital, especially for locomotion. In vertebrates the most strategic receptor is that for acetylcholine, the nicotinic receptor. In view of the breadth of action of the various conotoxins it is perhaps not surprising that alpha-conotoxin binds selectively to the nicotinic receptor. It is entirely possible that similar blockers exist for the receptors which are vital to locomotion in lower species. As mentioned previously, lophotoxin effects vertebrate neuromuscular junctions. It appears to act on the end plate region of skeletal muscle (79,59), to block the nicotinic receptor at a site different from the binding sites for other blockers (81). 

Maskos, U., Molles, B.E., Pons, S. et al. Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors. Nature. 436 103, 2005. 

Narahashi T, Aistrup GL, Marszalec W and Nagata K (1999). Neuronal nicotinic acetylcholine receptors A new target site for ethanol. Neurochemistry International, 35, 131-141. 

Metabolism of Other Pharmacologically Active Compounds by Cytochrome P450 Enzymes 449 Future Targets for Candidate Gene Studies 450 Genome Scans to Investigate Tobacco Dependence 450 Genomic Areas Linked with Susceptibility to Nicotine Dependence 451... 

Both nicotinic and muscarinic receptors are widespread in the CNS. Muscarinic receptors with a high affinity for pirenzepine (PZ), M, receptors, predominate in the hippocampus and cerebral cortex, whereas M2 receptors predominate in the cerebellum and brainstem, and M4 receptors are most abundant in the striatum. Central muscarinic and nicotinic receptors are targets of intense pharmacological interest for their potential roles in regulating abnormal neurological signaling in Alzheimer s disease, Parkinson s disease and certain seizure disorders. Nicotinic receptors are largely localized at prejunctional sites and control the release of neurotransmitters [10,11],... 

Nicotine is an agonist at the nicotinic acetylcholine receptor (nAChR). Activation of this receptor depolarizes target cells (see Ch. 11). nAChRs are composed of five subunits surrounding a central ion-channel pore. Twelve different nicotinic receptor subunits are expressed in the nervous system (a2-oclO and (32—134). Of these, a subset is expressed in the VTA (a3-a7 and P2—134). It is thought that a7 receptors form homomeric receptors a3, a4 and a6 form heteromeric channels with 02 or 04 and a5 and 03 can associate with other a/0 pairs. Studies in knockout mice implicate several subunits in the ability of nicotine to modulate dopamine neurons (a4, a6, a7, 02, 03) but... 

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