centrophenoxine, cholinergic nootropic

Centrophenoxine

  • Vitamins & Supplements
  • Updated December 18, 2017

Centrophenoxine, also known as meclofenoxate, has been used as a dietary supplement for its potential memory-boosting abilities. It has properties similar to acetylcholine, which is a neurotransmitter important to memory and learning. However, clinical evidence is weak and many studies have shown a lack of cognitive benefit. Most studies have reported that side effects with centrophenoxine are mild, but a few testing the active component of centrophenoxine (DMAE; dimethylethanolamine) have raised safety concerns.

Evidence

Although multiple clinical trials have tested the effects of centrophenoxine, the studies were of suboptimal quality and the results were inconclusive.

Our search identified:

  • 0 meta-analyses or systematic reviews
  • 6 randomized clinical trials 3 in dementia patients, 2 in healthy elderly people, and 1 in head trauma patients
  • Numerous preclinical studies on possible mechanisms of action

Potential Benefit

The clinical evidence for centrophenoxine is weak and inconclusive. The largest and most well-carried out study was a double-blind randomized control trial of 74 healthy elderly people that examined the effects of a 9-month centrophenoxine treatment on cognitive functions [1]. Following treatment, the centrophenoxine group performed significantly better than placebo on one measure of memory called delayed free recall, which was related to consolidation of new information into long-term memory. But there were no treatment effects on the five other measures of memory tested. Another smaller double-blind clinical study in 28 people with memory deficits reported that 3 weeks of centrophenoxine treatment did not show statistically significant effects on any of the 8 measures of memory or mental concentration [2]. More recently, a randomized controlled trial of 242 patients with mild cognitive impairment tested the effects of DMAE, which is the active component of centrophenoxine [3]. The study found no significant difference in memory, executive function, or attention between the treatment and placebo groups after 24 weeks.

Preclinical studies have shown that centrophenoxine improves learning and memory in aged animals [4] and those with memory impairment [5-7] or stroke [8]. These benefits may be due to centrophenoxine's ability to decrease inflammation [8], oxidative stress [9][10], and levels of damaged proteins and lipids in the brain [11]. However, these potential benefits have not been confirmed in humans.

For Dementia Patients

Clinical trials in dementia patients are of suboptimal quality and did not produce valid findings. A randomized controlled trial of 50 dementia patients examined the effects of centrophenoxine treatment, but the data could not be analyzed rigorously and therefore the results were inconclusive [12]. Another clinical trial of 63 mild-to-moderate Alzheimer's patients compared the effects of centrophenoxine alone with a combination treatment that included centrophenoxine [13]. Because there was no placebo control, it is unclear whether the improvement in cognitive functions was due to centrophenoxine.

Safety

Most studies have reported that side effects with centrophenoxine are mild, including nausea, headache, dizziness, gastrointestinal issues, and mild stimulant effects [12][13]. However, a few studies testing DMAE, the active component of centrophenoxine, have raised safety concerns. A clinical trial testing DMAE in 242 Alzheimer’s disease patients had 3 serious adverse events including cardiac failure leading to death, cardiac arrest, and seizure [3]. The investigators could not exclude the possibility that these events were related to DMAE. In preclinical studies, DMAE has produced neural tube defects and therefore should be avoided by women of child-bearing age [14]. Drug interactions with centrophenoxine are unknown, but it should not be used in people with severely high blood pressure [15].

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

How to Use

Centrophenoxine is available over the counter in capsules that contain 200–300 mg each. Clinical trials that tested the effects of centrophenoxine on cognitive functions have used daily doses of 1,200 mg in healthy elderly and doses of up to 2,000 mg in dementia patients [1-3][12][13].

Learn More

Evaluation of centrophenoxine's potential biological effects from Examine.com

Quality Control of Sources: United States Pharmacopeial Convention (USP) and FDA Information on Dietary Supplements offer information on the quality of specific supplements and can assist in finding a trusted brand.

References

  1. Marcer D, Hopkins SM (1977) The differential effects of meclofenoxate on memory loss in the elderly. Age Ageing 6, 123-131.
  2. Oliver JE, Restell M (1967) Serial testing in assessing the effect of meclofenoxate on patients with memory defects. Br J Psychiatry 113, 219-222.
  3. Dubois B, Zaim M, Touchon J et al. (2012) Effect of six months of treatment with V0191 in patients with suspected prodromal Alzheimer's disease. J Alzheimers Dis 29, 527-535.
  4. Mosharrof AH, Petkov VD, Petkov VV (1987) Effects of meclofenoxate and citicholine on learning and memory in aged rats. Acta Physiol Pharmacol Bulg 13, 17-24.
  5. Petkov VD, Mosharrof AH, Petkov VV (1988) Comparative studies on the effects of the nootropic drugs adafenoxate, meclofenoxate and piracetam, and of citicholine on scopolamine-impaired memory, exploratory behavior and physical capabilities (experiments on rats and mice). Acta Physiol Pharmacol Bulg 14, 3-13.
  6. Voronina TA, Garibova TL, Trofimov SS et al. (1991) Comparative studies on the influence of ONK (N(5-hydroxynicotinoil) glutamic acid), piracetam and meclofenoxate on the learning- and memory-impairing effect of scopolamine, clonidine, and methergoline. Acta Physiol Pharmacol Bulg 17, 8-16.
  7. Nehru B, Bhalla P, Garg A (2006) Evidence for centrophenoxine as a protective drug in aluminium induced behavioral and biochemical alteration in rat brain. Mol Cell Biochem 290, 33-42.
  8. Liao Y, Wang R, Tang XC (2004) Centrophenoxine improves chronic cerebral ischemia induced cognitive deficit and neuronal degeneration in rats. Acta Pharmacol Sin 25, 1590-1596.
  9. Zs-Nagy I (1989) On the role of intracellular physicochemistry in quantitative gene expression during aging and the effect of centrophenoxine. A review. Arch Gerontol Geriatr 9, 215-229.
  10. Sharma D, Maurya AK, Singh R (1993) Age-related decline in multiple unit action potentials of CA3 region of rat hippocampus: correlation with lipid peroxidation and lipofuscin concentration and the effect of centrophenoxine. Neurobiol Aging 14, 319-330.
  11. Glees P, Spoerri PE (1975) [Centrophenoxin-induced dissolution and removal of lipofuscin. An electron microscopic study (author's transl)]. Arzneimittelforschung 25, 1543-1548.
  12. Pek G, Fulop T, Zs-Nagy I (1989) Gerontopsychological studies using NAI ('Nurnberger Alters-Inventar') on patients with organic psychosyndrome (DSM III, Category 1) treated with centrophenoxine in a double blind, comparative, randomized clinical trial. Arch Gerontol Geriatr 9, 17-30.
  13. Popa R, Schneider F, Mihalas G et al. (1994) Antagonic-stress superiority versus meclofenoxate in gerontopsychiatry (alzheimer type dementia). Arch Gerontol Geriatr 19 Suppl 1, 197-206.
  14. Fisher MC, Zeisel SH, Mar MH et al. (2002) Perturbations in choline metabolism cause neural tube defects in mouse embryos in vitro. FASEB J 16, 619-621.
  15. Possemato R, Marks KM, Shaul YD et al. (2011) Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 476, 346-350.