Acetylcholine receptors decreased

Qll The number of normal acetylcholine receptors decreases as the disease progresses. This reduces the effectiveness of anticholinesterases. In such cases, immunosuppressant therapy, using a corticosteroid, can be used. This will help to reduce the formation of antibodies to acetylcholine receptors. In... 

Eldefrawi, A.T. and Eldefrawi, M.E. Phencyclidine interactions with the ionic channel of the acetylcholine receptor and elec-trogenic membrane. Proc Natl Acad Sci USA 77 1224-1228, 1980. Ary, T.C. and Komiskey, H.L. Basis of phencyclidine s ability to decrease the synaptosomal accumulation of 3H-catecholamines. 

Fluorine has been used to modulate the basicity of amines which may lead to an improvement in brain exposure. Recently, the discovery of a series of a4(32 nicotinic acetylcholine receptor (nAChR) potentiators as possible treatment for Parkinson s disease and schizophrenia was were disclosed [40]. Optimization of isoxazole 40 included the bioisosteric replacement of the central amide by an imidazole ring. Introduction of a fluorine at the 6-position of the phenyl ring provided compound 41. This compound had excellent potency but was determined to be a substrate for P-gp (efflux ratio >10). In an attempt to reduce amine basicity and decrease the efflux propensity, the 4-fluoropiperidine 42 was identified which retained potency and had significantly reduced P-gp efflux liability (efflux ratio 1). CNS penetration of 42 was observed in rodents following intraperitoneal (IP) treatment at 5mg/kg and showed a brain concentration of 6.5 gM. 

Histaminergic neurons can regulate and be regulated by other neurotransmitter systems. A number of other transmitter systems can interact with histaminergic neurons (Table 14-1). As mentioned, the H3 receptor is thought to function as an inhibitory heteroreceptor. Thus, activation of brain H3 receptors decreases the release of acetylcholine, dopamine, norepinephrine, serotonin and certain peptides. However, histamine may also increase the activity of some of these systems through H, and/or H2 receptors. Activation of NMDA, p opioid, dopamine D2 and some serotonin receptors can increase the release of neuronal histamine, whereas other transmitter receptors seem to decrease release. Different patterns of interactions may also be found in discrete brain regions. 

The effect of Li+ upon the synthesis and release of acetylcholine in the brain is equivocal Li+ is reported to both inhibit and stimulate the synthesis of acetylcholine (reviewed by Wood et al. [162]). Li+ appears to have no effect on acetyl cholinesterase, the enzyme which catalyzes the hydrolysis of acetylcholine [163]. It has also been observed that the number of acetylcholine receptors in skeletal muscle is decreased by Li+ [164]. In the erythrocytes of patients on Li+, the concentration of choline is at least 10-fold higher than normal and the transport of choline is reduced [165] the effect of Li+ on choline transport in other cells is not known. A Li+-induced inhibition of either choline transport and/or the synthesis of acetylcholine could be responsible for the observed accumulation of choline in erythrocytes. This choline is probably derived from membrane phosphatidylcholine which is reportedly decreased in patients on Li+ [166],... 

Mecamylamine is a noncompetitive antagonist at the nicotinic acetylcholine receptor site. If mecamylamine could effectively block the physiological and reinforcing effects of cigarette smoking, this should, in theory, lead to eventual extinction of the behavior. When mecamylamine is administered to smokers, it has increased rather than decreased ad libitum smoking behavior, presumably due to smokers... 

Mechanism of Action A urinary antispasmodic t hat act s as a direct antagonist at muscarinic acetylcholine receptors in cholinergically innervated organs. Reduces tonus (elastictension) of smooth muscle in the bladder and slows parasympathetic contractions. Therapeutic Effect Decreases urinary bladder contractions, increases residual urine volume, and decreases detrusor muscle pressure. 

One of the best-understood autoimmune diseases is myasthenia gravis, a condition associated with a decrease in the number of functional post-synaptic nicotinic acetylcholine receptors (Fig. 30-23) in neuromuscular junctions. e The resulting extreme muscular weakness can be fatal. Myasthenia gravis is not rare and affects about one in 10,000 peopled An interesting treatment consists of the administration of physostigmine, diisopropyl-phosphofluoridate (Chapter 12, Section C,l), or other acetylcholinesterase inhibitors (Box 12-E). These very toxic compounds, when administered in controlled amounts, permit accumulation of higher acetylcholine concentration with a resultant activation of muscular contraction. The same compounds... 

Myasthenia gravis is an autoimmime disease that affects the neuromuscular junction.A decrease in the number of available acetylcholine receptors due to circulating antibodies results in impaired neuromuscular transmission. This impairment manifests clinically as weakness and fatigability of volimtary musculature. Ocular and other muscles innervated by cranial nerves are most often involved. Although different treatment modalities are available, anticholinesterase drugs remain the mainstay of therapy. 

Catalpol. Zhang et al. [233] studied the neuroprotective effects of catalpol, an iridoid glycoside isolated from the fresh rehmannia roots, on the cholinergic system and inflammatory cytokines in the senescent mouse brain induced by D-galactose. Acetylcholinesterase (AChE) activity increased in senescent mouse brain and choline acetyltransferase (ChAT) decreased in the basal forebrain of senescent mouse. Muscarinic acetylcholine receptor Ml (mAChRl) expression declined and the levels of tumor necrosis factor (TNF-a), interleukin-ip (IL-ip), and advanced glycation end products... 

Ohno K, Wang HL, Milone M et al 1996 Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit. Neuron 17 157-170... 

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