Cholinergic receptors mechanisms

EEG slow waves. The differential EEG and ACh responses to dialysis delivery of AF-DX 116 (M2/M4) versus pirenzepine (M1/M4) supports the conclusion that, in B6 mouse, postsynaptic muscarinic receptors of the Ml subtype form one receptor mechanism by which ACh activates the EEG (Douglas et al, 2002a). The data summarized in Fig. 5.11 provide direct measures of G protein activation in basal forebrain and prefrontal cortex by muscarinic cholinergic receptors (DeMarco et al, 2004). The in vitro data of Fig. 5.11A indicate the presence of functional muscarinic receptors in regions of B6 mouse prefrontal cortex where in vivo microdialysis studies (Douglas et al, 2002a, b) revealed modulation of ACh release and EEG by pre- and postsynaptic muscarinic receptors (Figs. 5.9 and 5.10). 

Zarrindast MR, Pazouki M, Nassiri-Rad S. (1997). Involvement of cholinergic and opioid receptor mechanisms in nicotine-induced antinociception. Pharmacoi Toxicoi. 81(5) 209-13. 

Schechter MD (1995) Scopolamine-physostigmine combination does not substitute for nicotine. Prog Neuropsychopharmacol Biol Psychiatr 19 499-508 Schechter MD, Meehan SM (1992) Further evidence for the mechanisms that may mediate nicotine discrimination, Pharmacol Biochem Behav 41 807-812 Schechter MD, Rosecrans JA (197 la) Behavioral evidence for two types of cholinergic receptor in the C,N,S, Eur J Pharmacol 15 375-378... 

Nicotinic cholinergic receptors are located on cells that release a wide variety of transmitters (see chapter by Barik and Wonnacott, in this volume), so that nicotine interacts with multiple neurochemical pathways. The roles of cholinergic, dopaminergic, and endogenous opioid systems in physical dependence and withdrawal have been most thoroughly studied and documented. Research on the role of other transmitters and neurochemical mechanisms is rather scattered. Overall, however, research with rodent models of physical dependence has provided a wealth of potential targets for experimental treatments to aid smoking cessation. 

Other mechanisms, such as the inhibition of -amyloid formation. There are several other alkaloids which are nicotinic agonists at the cholinergic receptor such as lobeline (89) from Lobelia inflata. Lobelia inflata a could be exploited to influence cholinergic function in AD. Sophoramine (90) and cytisine (91), found in members of the Leguminosae, have nicotinic actions but they do not appear to have been developed for any pharmaceutical purposes, probably because of their toxicity. 

Thiotropium Mechanisms competitive inhibition of muscarinic cholinergic receptors, reduces intrinsic vagal tone to the airways may decrease gland secretion, may block reflex broncho-constriction secondary to irritants or to reflux esophagitis ... 

Mechanism of Action A cholinergic that acts directly at cholinergic receptors in the smooth muscle of the urinary bladder and GI tract. Increases detrusor muscle tone. Therapeutic Effect May initiate micturition and bladder emptying. Improves gastric and intestinal motility. 

Mechanism of Action Aweakanticholinergicthat exhibits competitive antagonism of acetylcholine at cholinergic receptors in the corpus striatum, which restores balance. Therapeutic Effect Antiparkinson activity... 

Mechanism of Action A smoking deterrent that inhibits acetylcholine at the auto-nomicganglia. Blocks central nicotinic cholinergic receptors, which inhibits effects of nicotine. Therapeutic Effect Reduces blood pressure decreases desire to smoke. Pharmacokinetics Completely absorbed following PO administration. Widely distributed. Excreted in urine. Half-life 24 hr. 

Until recently, little attention had been paid to nicotinic mechanisms in explaining either the pathophysiology or treatment of AD. Patients with AD have a marked reduction in cortical nicotinic cholinergic receptor binding compared with that of age-matched control subjects (Aubert et al. 1992 Flynn and Mash 1986 Whitehouse et al. 1986). Psychiatrically healthy elderly subjects show an age-related decline in cortical nicotinic binding (Flynn and Mash 1986). 

Pharmacodynamics What the drug does to the body. The mechanisms of action exerted by the drug such as cholinergic receptor blockade (e.g., benztropine). 

Both stimulant users and smokers may down-regulate their dopamine receptors because of excessive dopamine stimulation. However, nicotine users may up-regulate their nicotinic cholinergic receptors to help compensate for the fact that nicotine keeps turning them off (Fig. 13—20). These possible changes in dopamine and nicotine receptors may be related to the psychopharmacological mechanisms underlying nicotine s profound ability to produce dependence and withdrawal. 

FIGURE 19-1 T Mechanism of action of cholinergic stimulants. Direct-acting stimulants bind directly to the postsynaptic cholinergic receptor. Indirect-acting stimulants inhibit the cholinesterase enzyme, thus allowing acetylcholine to remain in the synaptic cleft. 

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