Cholinergic enhancement

REM sleep (Kodama et al, 1990 Leonard Lydic, 1995, 1997) and cholinergic REM sleep enhancement (Lydic et al., 1991), ACh release is significantly increased in the same regions of the pontine reticular formation where microinjection of cholinomimetics enhances REM sleep (1.3 and 1.4 on Fig. 5.1). These results support the conclusion that at the level of ACh release, the cholinergic enhancement of REM sleep is a faithful model of spontaneous REM sleep. 

A review of symptomatic therapeutic responses in AD to cholinergic-enhancing agents suggests that primary therapeutic effects include the focusing... 

THE CHOLINERGIC HYPOTHESIS OF ALZHEIMER S DISEASE AND CHOLINERGIC ENHANCEMENT STRATEGIES... 

Furey ML, Pietrini P, Haxby JV (2000) Cholinergic enhancement and increased selectivity of perceptual processing during working memory. Science 290(5500) 2315-2319. doi 10.1126/science.290.5500.2315... 

Saykin, A.J., et al.. Cholinergic enhancement of frontal lobe activity in mild cognitive impairment. Brain, 2004. 127(Pt 7) p. 1574-83. 

The compounds used to palliate the mnemonic and cognitive decline associated with dementia include cerebral vasodilators and the so-called nootropic agents. These materials enhance cerebral metaboHsm. Agents which enhance neurotransmitter function are in most cases cholinergic. 

Several cholinergic strategies, other than cholinesterase inhibition, have been employed with the intention of ameliora ting the symptoms of AD. These include precursor loading acetylcholine release enhancement, and direct activation of both muscarinic and nicotinic receptors. 

An alternative approach to stimulate cholinergic function is to enhance the release of acetylcholine (ACh). Compounds such as the aminopyridines increase the release of neurotransmitters (148). The mechanism by which these compounds modulate the release of acetylcholine is likely the blockade of potassium channels. However, these agents increase both basal (release in the absence of a stimulus) and stimulus-evoked release (148). 4-Aminopyridine [504-24-5] was evaluated in a pilot study for its effects in AD and found to be mildly effective (149). 

However, clinical results with compounds enhancing cholinergic function have not been overly convincing (272). In the case of tacriae, however, the beneficial therapeutic iadex was sufficient to justify regulatory approval ia several countries. Psychostimulants such as pemoline, amphetamine, procaine, and methylphenidate have failed to show cognitive enhancing effects ia patients with dementia, except possibly as iadirect consequences of mood elevation. 

Compounds that affect activities of hepatic microsomal enzymes can antagonize the effects of methyl parathion, presumably by decreasing metabolism of methyl parathion to methyl paraoxon or enhancing degradation to relatively nontoxic metabolites. For example, pretreatment with phenobarbital protected rats from methyl parathion s cholinergic effects (Murphy 1980) and reduced inhibition of acetylcholinesterase activity in the rat brain (Tvede et al. 1989). Phenobarbital pretreatment prevented lethality from methyl parathion in mice compared to saline-pretreated controls (Sultatos 1987). Pretreatment of rats with two other pesticides, chlordecone or mirex, also reduced inhibition of brain acetylcholinesterase activity in rats dosed with methyl parathion (2.5 mg/kg intraperitoneally), while pretreatment with the herbicide linuron decreased acetylcholine brain levels below those found with methyl parathion treatment alone (Tvede et al. 1989). 

Acetylcholine-mediated parasympathetic activity leads to production of the non-adrenergic-non-cholinergic transmitter nitric oxide. By enhancing the activity of guanylate cyclase, nitric... 

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