Nicotinic receptor agonists antagonists

Wiley JL, James JR, Rosecrans JA (1996) Discriminative stimulus properties of nicotine approaches to evaluating potential nicotinic receptor agonists and antagonists. Drug Dev Res 38 222-230... 

Figure 5. Cartoon of a cholinergic synapse showing major steps in the synthesis of acetylcholine. The two major receptor types, the ionotropic nicotinic receptor and the metabotropic muscarinic receptor, are shown (see also Chapter 1). Presynaptic muscarinic (M2) and nicotinic receptors are also depicted. Drugs which have been widely used to manipulate the cholinergic systems, and which are mentioned in the text, include the muscarinic receptor antagonists scopolamine and atropine and the nicotinic receptor agonist nicotine. Anticholinesterases (discussed elsewhere in this volume) include drugs such as physostigmine, rivastigmine, donepezil, and galanthamine.

Other approaches, some of which are still in clinical development, include restoration of the acetylcholine-dopamine balance in the basal ganglia, neuronal nicotinic receptor agonists, neurotrophic immunophilins, dopamine transport inhibitors, COMT-inhibitors, and adenosine A2A receptor antagonists.162,163 Also surgical therapies are used or under development, including stereotactic thalamotomy, continuous electric thalamus stimulation,164 posteroventral pallidotomy and transplantation of embryonal substantia nigra cells. 

Nondepolarizing blockade occurs when pure antagonists compete with agonists for nicotinic receptors. Because antagonists lack activity, there is no muscle contraction (fasciculations). Blockade is overcome by high concentrations of agonist (ACh). 

Acetyichoiine Lobeline acts as a partial agonist at nicotinic receptors. It displaces nicotine with a low nanomolar affinity in the rat brain (Damaj et al. 1997). Similar to nicotine, it may act as an antagonist through persistent activation and desensitization of the receptor (Briggs and McKenna 1998 Tani et al. 1998). Lobeline shows a greater affinity for the pZ subunit of the nicotinic receptor than jS4 subunits (Parker et al. 1989). 

Decker MW, Anderson DJ, Brioni ID, DonneUy-Roberts DL, Kang CH, O Neill AB, Piattoni-Kaplan M, Swanson S, SuUivan IP (1995) Erysodine, a competitive antagonist at neuronal nicotinic acetylcholine receptors, Eur J Pharmacol 280 79-89 Dekeyne A, Girardon S, MUlan Ml (1999) Discriminative stimulus properties of the novel serotonin (5-HT)2c receptor agonist, Ro 60-0175 a pharmacological analysis. Neuropharmacology 38 415-423... 

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