Galanthamine

Galantamine (trade names Razadyne, Razadyne ER, Reminyl, Nivalin, Memeron) is a drug developed by Janssen Pharmaceutica, and used for the treatment of mild to moderate Alzheimer’s disease. It is an alkaloid that is obtained synthetically from the bulbs and flowers of the Caucasian snowdrop (Voronov’snowdrop), Lycoris radiata (Red Spider Lily), Galanthus woronowii (Amaryllidaceae) and related species. The active ingredient was discovered accidentally by a Bulgarian pharmacologist in the 1950s.

Pharmacology
Galantamine in its pure form is a white powder. Galantamine is a competitive and reversible cholinesterase inhibitor. It is believed it works by enhancing cholinergic function by increasing the concentration of acetylcholine in the brain. The atomics resolution 3D structure of the complex of galantamine and its target, acetylcholinesterase, was recentely determined by X-ray crystallography. 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 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 7 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
The major route of metabolism for galantamine is through the liver, this accounts for approximately 75% of the total metabolism of galantamine. Hepatic cytochrome P450 (CYP) isoenzymes are the active enzymes for this metabolic route. In vitro studies have shown that 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.

Indications
Galantamine is indicated for 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 4mg, 8mg and 12mg forms. The capsules come in 8mg, 16mg, and 24mg forms. A new combination therapy of Galantamine and Alpha GPC has recently been released in 608mg capsules (Memeron).

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.

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 5 to 6 hours of deep sleep and practice an induction technique such as meditation, MILD or WILD  many people report more success with galantamine.

There are also reports that taking galantamine without proper induction technique will not lead to LD or OBE but will result in only a vivid dream instead. It should also be noted that due to a long half life Galantamine will stay in the body for a period of up to and over 48 hours, as such it is advisable to space out the use of Galantamine over a period of three days so that the body does not build a resistance to the drug ruining its effectiveness.

Galantamine used with choline bitartrate or Alpha-GPC can dramatically increase one's odds of becoming lucid. Some people report mixing galantamine with other nootropic can enhance the degree of lucidity, but this is still controversial since some mixtures may work for some people, but lead to failure for others.

Nootropic
Along with other cholinergics or acetylcholinesterase inhibitors such as Huperzine A, galantamine also has been used as nootropic or "brain enhancer".

Caution
The FDA and other international health authorities have published an alert on galantamine based data from use on two studies during the treatment of mild cognitive impairment; higher mortality rates were seen in drug-treated patients.

Total synthesis
Galantamine is produced from natural resources and a patented total synthesis process. Many other synthetic methods exist but have not been implemented on an industrial scale.