Nicotinic receptor family

The nicotinic receptor (nAChR) comprises a family of receptor subtypes that respond to the neurotransmitter acetylcholine (ACh) and the tobacco alkaloid nicotine. 

The skin of neotropical frogs of the Dendrobatidae family has been a rich source of bioactive compounds [42] such as the alkaloids epibatidine, batrachotoxins, histrionicotoxin, and indolizidines. The latter have been investigated due to their activity as noncompetitive blockers of the nicotinic receptor channels [43]. Because only small amounts are available and due to their pronounced physiological activity, these alkaloids are important targets for organic synthesis [44]. Since... 

Nomicotine, an organocatalyst studied by Dickerson and co-workers (Entry 5 [52, 58d], Appendix 7.B), reinforces the important principle that even catalysts from Nature can present problems when it comes to toxicity. The family of nicotinic receptor agonists (Figure 7.9) contains several chiral pyrrolidines and piperidines with the potential to act as asymmetric aldol catalysts. Nomicotine, which can be isolated from plants such as tobacco, or readily synthesized by demethylation of the maj or tobacco alkaloid nicotine, was investigated in some depth as an aldol catalyst by Dickerson and Janda in 2002 [52]. 

Galantamine, unlike the other anticholinesterases in clinical use, is derived from the alkaloids from the daffodil and snowdrop family. It is a reversible, competitive inhibitor of acetylcholinesterase with some inhibitory action on butyryl cholinesterase. It is also an agonist at nicotinic receptor sites. Although a clinically effective drug, galantamine frequently causes gastrointestinal side effects. 

Two families of cholinoceptors, designated muscarinic and nicotinic receptors, can be distinguished from each other on the basis of their different affinities for agents that mimic the action of acetylcholine (cholinomimetic agents). 

Xu J, Pato MT, Dalla Torre C, Medeiros H, Carvalho C, et al. 2001. Evidence of linkage disequilibrium between the alpha 7-nicotinic receptor gene (CHRNA7) locus and schizophrenia in Azorean families. Am J Med Gen 105 669-674. 

Another important family of ligand gated ion channels is the receptors for the excitatory amino acid neurohansmitters such as glutamate and aspartate (Figure 10.8). These act as neurotransmitters at the vast majority of excitatory synapses in the brain. These receptors are also multisubunit ion channel arrays, in this case consisting of tehamers of related subunits (Wollmuth and Sobolevsky, 2004). The proteins that make up these subunits are all related in structure but are quite different from those that make up the nicotinic and GABA-A receptor family. 

As well as hallucinations and delusions, schizophrenia is characterized by deficits in information processing. Schizophrenics have difficulty suppressing irrelevant environmental stimuli. This is referred to as sensory gating or prepulse inhibition, and commonly measured with auditory evoked potentials. When two stimuli, such as sounds, are presented within 30-500 msec, the response to the second stimulus rapidly decreases upon repeated presentations in healthy people, but not in persons with schizophrenia (Braff et al., 2001). This deficit is found in family members of patients with schizophrenia, and has been linked to the alpha-7 nicotinic receptor gene. The deficit is reversed by nicotine on an acute basis, and by some antipsychotic drugs. Alpha-7 nicotinic agonists are under development as treatment for schizophrenia (Martin et al., 2004). 

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