Mixing Memory-Enhancing Nootropics

Can Galantamine be taken with Deprenyl and / or Centrophenoxine?

SHIRLEY, Sequim, WA

A. Short answer — yes, they can all be taken simultaneously. They all act differently on several neurotransmitter systems. There are no adverse interactions between Galantamine, Deprenyl, or Centrophenoxine.

A more detailed answer follows.

Figure 1. Survival curves of old male rats treated with deprenyl (n = 22) or saline (n = 22). The rats were grouped according to sexual activity (A — sexually active; B — able to mount, but unable to ejaculate; C — sluggish, non-copulators). Note that sexually active members of each group lived the longest; and that all members of the saline-treated group died before any of the rats treated with Deprenyl died. This study helped to earn Deprenyl the reputation of being the anti-aging aphrodisiac.
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Deprenyl is usually considered to act as a monoamine oxidase B inhibitor. Mono­amine oxidase B is an enzyme that ­metabolizes the stimulatory dopa­min­ergic neurotransmitters, ep­i­neph­rine and norepinephrine. By inhibiting this enzyme, Deprenyl increases the levels of these neurotransmitters in the brain.

However, perhaps more importantly (but less well known), is that Deprenyl also increases dopaminergic receptor sensitivity, thereby enhancing the effect of the dopaminergic neurotransmitters. Since the degenerative changes in the brain that cause Parkinson’s disease take place to some degree in all of us as we get older, scientists have said that if we live long enough we will all get Parkinson’s disease. It’s reassuring to know something can prevent or reverse this process. Deprenyl has been shown to be a pre-eminent life-extending substance. Dr. Joseph Knoll, one of the developers of Deprenyl, reported dramatic lifespan extension of male Fischer-344 rats treated with the drug (See Figure 1).1 Subsequent studies confirmed these earlier results.2,3

Figure 2. Life-extending effect of DMAE on old A/J mice. Treatment started at 21 months of age. The maximum lifespan of the mice is about 30 months.
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Centrophenoxine is generally considered to increase the formation of the neurotransmitter acetylcholine in the brain. Alzheimer’s disease is characterized as being due to a deficiency of acetylcholine. It also has a number of other beneficial effects, including acting as a mild cerebral stimulant, maintaining membrane fluidity, and inhibiting lipofuscin (aging pigment) formation. Centrophenoxine is chemically very similar to DMAE (dimethyl­aminoethanol). Consequently, I think Centrophenoxine and DMAE can be used interchangeably. Centrophenoxine is probably longer-acting than DMAE, but DMAE is considerably less expensive. Dr. Richard Hochschild evaluated the potential life-extending effect of DMAE on old mice. He administered DMAE in the drinking water to 21 month-old A/J mice. The DMAE-fed mice experienced a significant reduction in mortality and an increase in both mean and maximum survival (Fig. 2).4 I presume that Centrophenoxine would produce similar life-extending results.

Figure 3. Alzheimer’s patients taking galantamine had 70% fewer deaths than Alzheimer’s patients taking placebo.
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As mentioned, Alzheimer’s disease has been characterized as being due to a deficiency of acetylcholine. The beneficial effects of Galantamine are generally believed to result from its ability to prevent the breakdown of acetylcholine by inhibiting the enzyme acetylcholinesterase, which metabolizes acetylcholine. However, Galantamine also enhances the function of nicotinic receptors in the cholinergic system, providing a dual mechanism of action — i.e., it not only increases the levels of acetylcholine in the brain, but also enhances cholinergic and nicotinic receptor sensitivity.5,6

Of particular interest are two studies that showed treatment of Alzheimer’s patients with Galantamine resulted in decreased overall mortality (Fig. 3)7 and lower levels of cardiovascular disease and death from all causes!8 These studies were previously discussed in detail in two articles in Life Enhancement (See “Galantamine Cuts Mortality” and “Galantamine Slashes Heart Attacks and Death” in the April and August, 2013 issues, respectively.)

Consequently, the combination of substances that you suggested would appear to act synergistically for not only cognitive enhancement, but life-extending effects, as well.

Sincerely,

Ward Dean, M.D.

References

  1. Knoll J. The striatal dopamine dependency of lifespan in malae rats. Longevity study with (-)Deprenyl. Mech Ageing Dev. 1988 Dec;46(1-3):237-62.
  2. Milgram NW, Racine RJ, Nellis P, Mendonca A, Ivy GO. Maintenance on L-deprenyl prolongs life in aged male rats. Life Sci. 1990;47(5):415-20.
  3. Carillo MC, Kanai S, Sato Y, Ivy GO, Kitani K. Chronic treatement of (-) deprenyl prolongs the life span of male Fischer 344 rats. Oral presentation, American Aging Association Conference, Oct 19th, 1992, University of Nebraska.
  4. Hochschild R. Effect of dimethylaminoethanol on the life span of senile male A/J mice. Exp Gerontol. 1973 Aug;8(4):185-91.
  5. Maelicke A, Samochocki M, Jostock R, Fehrenbacher A, Ludwig J, Albuquerque EX, Zerlin M. Allosteric sensitization of nicotinic receptors by galantamine, a new treatment strategy for Alzheimer’s disease. Biol Psychiatry. 2001;49:279-88.
  6. Coyle J, Kershaw P. Galantamine, a cholinesterase inhibitor that allosterically modulates nicotinic receptors: effects on the course of Alzheimer’s disease. Biol Psychiatry. 2001;49:289-99.
  7. Hager K, Baseman AS, Nye JS, Brashear HR, Han J, Sano M, Davis B, Richards HM. Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer’s disease. Neuropsychiatr Dis Treat. 2014 Feb 21;10:391-401.
  8. Nordström P, Religa D, Wimo A, Winblad B, Eriksdotter M. The use of cholinesterase inhibitors and the risk of myocardial infarction and death: a nationwide cohort study in subjects with Alzheimer’s disease. Eur Heart J. 2013 Sep;34(33):2585-91.

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