Galantamine 357-70-0

Pharmacology

Galantamine in its pure form is a white powder. Galantamine is a competitive and reversible cholinesterase inhibitor. It reduces the action of AChE and therefore tends to increase the concentration of acetylcholine in the brain. It is hypothesized that this action might relieve some of the symptoms of Alzheimer'sThe atomic resolution 3D structure of the complex of galantamine and its target, acetylcholinesterase, was determined by X-ray crystallography in 1999 (PDB code: [/1dx6 see complex]). There is no evidence that galantamine alters the course of the underlying dementing process. Galantamine has also shown activity in modulating the nicotinic cholinergic receptors on cholinergic neurons to increase acetylcholine release.

Pharmacokinetics

Absorption of galantamine is rapid and complete and shows linear pharmacokinetics. It is well absorbed with absolute oral bioavailability between 80 and 100%. It has a half-life of seven hours. Peak effect of inhibiting acetylcholinesterase was achieved about one hour after a single oral dose of 8 mg in some healthy volunteers. Plasma protein binding of galantamine is about 18%, which is relatively low.

Metabolism

Approximately 75% of a dose of galantamine is metabolised in the liver. In vitro studies have shown that Hepatic CYP2D6 and CYP3A4 are involved in galantamine metabolism. For Razadyne ER (the once-a-day formulation), CYP2D6 poor metabolizers had drug exposures that were approximately 50% higher than for extensive metabolizers. About 7% of the population has this genetic mutation, however because the drug is individually titrated to tolerability, no specific dosage adjustment is necessary for this population.

Clinical use

Indications

Galantamine is indicated for the treatment of mild to moderate Vascular Dementia and Alzheimer's.

Available forms

The product is supplied in twice-a-day tablets, once-a-day extended release capsules, and in oral solution. The tablets come in 4 mg, 8 mg, and 12 mg forms. The capsules come in 8 mg, 16 mg, and 24 mg forms.

Adverse events

In clinical trials, galantamine's side effect profile was very similar to that of other cholinesterase inhibitors, with gastrointestinal symptoms being the most notable and most commonly observed. In practice, some other cholinesterase inhibitors might be better tolerated; however, a careful and gradual titration over more than three months may lead to equivalent long-term tolerability.

Other uses

Supplement for lucid dream and out-of-body experience

Some people who practice lucid dream (LD) or out-of-body experience (OBE) use galantamine to increase their odds to achieve LD or OBE. By taking small amount of galantamine (around 4 to 8 mg) after five to six hours of deep sleep and practice an induction technique such as meditation, MILD or WILD [

accessdate=2007-10-29