Cholinergic function, enhancing

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. 

Pharmacology Galantamine is a competitive and reversible inhibitor of acetylcholinesterase. While the precise mechanism of galantamine s action is unknown, it may exert its therapeutic effect by enhancing cholinergic function. Pharmacokinetics ... 

Pharmacology Donepezil enhances cholinergic function by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase (AChE). Donepezil s effect may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact. Pharmacokinetics ... 

Mechanism of Action A cholinesterase inhibitor that enhances and prolongs cholinergic function by increasing the concentration of acetylcholine through inhibition of f he hydrolysis of acefylcholine. Therapeutic Effect Increases muscle strength in myasthenia gravis. 

Mechanism of Action A cholinesterase inhibitor that inhibits the enzyme acetylcholinesterase, thus increasing the concentration of acetylcholine at cholinergic synapses and enhancing cholinergic function in the CNS. Therapeutic Effect Slows the progression of Alzheimer s disease. 

Enhancing cholinergic function in the brain by increased supply of the biological precursors of acetylcholine, lecithin or choline, similar to the treatment of Parkinson s disease with L-dopa, the precursor of dopamine. This approach, which was tried in dozens of short- and long-term studies, proved to be unsuccessful (Becker and Giacobini, 1988). 

Donepezil is primarily a reversible inhibitor of acetylcholinesterase with a long elimination half-life. It lacks the hepatotoxicity of tacrine but frequently causes nausea, vomiting and diarrhoea. These side effects, together with occasional bradycardia, sycope and changes in the sleep architecture, are directly associated with a central and peripheral enhancement of cholinergic function. At the present time, donepezil is the most widely prescribed anticholinesterase in the United States and Europe. 

Use To improve memory in mild to moderate Alzheimer s dementia. Drug enhances cholinergic function. Half-life 1.5-3.5 hours Onset Peaks Duration 1 hour 4 hours 12 hours... 

Galantamine is a cholinesterase (AChE) that enhances cholinergic function by increasing acetylcholine. It is indicated in the treatment of mild to moderate dementia of the Alzheimer type. 

Yamazaki, Y. Mamaue. N.. and Sumikawa. K. (2002). Nicotine compensaic.s for the loss of cholinergic function to enhance long-term potentiation induction. Brain Res. 946, 148-152. 

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. 

---