anticholinergic effect of DMAE?
I read DMAE can have that effect in the liver or blood, I do not remember, but not in the brain.
do you have any reference please? I am interested
I assume that this is in reference to a previous AOR post:
... the cognition-enhancing effects of DMAE are pretty questionable outside of ADD sufferers, although it does yield a stimulative effect; a recent study (PNAS 101(7):2140-4) did offer a mechanistic basis for hypothesizing a benefit if taken at night, especially if you're taking a lot of pro-cholinergic cognitive support supplements (due, ironically, to its possible anticholinergic effect).
A variety of studies suggest that DMAE exerts some form of anticholinergic effect. It does not itself appear to be a substrate for acetylcholine (ACh) synthesis in
vivo, and it appears that administration of DMAE results in the paradoxical situiation of increased brain choline with no corresponding increase in ACh. Several relevant references are appended; see especially:
Jope RS, Jenden DJ. Dimethylaminoethanol (deanol) metabolism in rat brain and its effect on acetylcholine synthesis. J Pharmacol Exp Ther. 1979 Dec;211(3):472-9.
[DMAE] increased the concentration of choline in the plasma and brain but did not alter the concentration of acetylcholine in the brain.Zahniser NR, Chou D, Hanin I. Is 2-dimethylaminoethanol (deanol) indeed a precursor of brain acetylcholine? A gas chromatographic evaluation. J Pharmacol Exp Ther. 1977 Mar;200(3):545-59.
After deanol administration, we were able to detect deanol in tissue and have attempted to determine a relationship between these levels and values of ACh in the same tissue. Regardless of deanol pretreatment time (1-30 minutes) or doses (33.3-3000 mg/kg i.p.) used, we detected no increase in mouse whole brain ACh levels. Likewise, there was no detectable elevation in ACh levels in rat whole brain, cortex, striatum or hippocampus after a 15-minute pretreatment with 550 mg/kg of deanol (i.p.). The only elevation in ACh levels which we detected occurred selectively in the striatum of mice pretreated with a massive dose (900 mg/kg i.p.) of deanol for 30 minutes. Obviously, no one is going to take the scaled equivalent of 900 mg/kg DMAE
orally, let alone intraperitoneally.
An anticholinergic effect is also consistent with three other facts:
- DMAE has a very well-established stimulative effect, whereas several antidepressants work exactly because they have an anticholinergic mechanism;
- DMAE does not appear to be useful in improving cognitive function in age-associated cognitive decline or Alzheimer's disease, but it
is effective (at the right dose etc) in ADD. Of course, the best-established drug for ADD is methylphenidate/Ritalin, which works through an anticholinergic effect.
- DMAE lowers the threshold of toxicity against curare, a deadly arrow poison used by some South American indigenous peoples, which kills because it is a natural ACh receptor inhibitor (this according to Lewis & Young, "Deanol and methylphenidate in minimal brain dysfunction" (Clin Pharmacol Ther 17(5):534-40), who advance this argument. On this fact, they reference Murphree et al, "2-Dimethylaminoethanol as a central nervous system stimulant -- one aspect of the pharmacology of reserpine. Res Publ Assoc Nerv Ment Dis. 1957;37:204-16).
Lewis & Young argue that DMAE may exert anticholinergic action by acting as a substrate for choline acetylase, producing acetyl-DMAE "as a false transmitter that actually interferes with central cholinergic function." It is also possible that it is simply acting as a competitive inhibitor, thereby reducing the synthesis of ACh.
This does not mean that DMAE is a useless supplement; it just means that its mechanism of action is not what it is often claimed to be. It certainly works well as a neurostimulative supplement for most, is useful for ADD, and (as previously noted) PNAS 101(7):2140-4 may offer "a mechanistic basis for
hypothesizing a benefit if taken at night, especially if you're taking a lot of pro-cholinergic cognitive support supplements".
Gais S, Born J.
Low acetylcholine during slow-wave sleep is critical for declarative memory consolidation.
PNAS. 2004 Feb 17;101(7):2140-4.
The neurotransmitter acetylcholine is considered essential for proper functioning of the hippocampus-dependent declarative memory system ... During slow-wave sleep (SWS), however, declarative memory consolidation is particularly strong, while acetylcholine levels in the hippocampus drop to a minimum. Observations in rats led to the hypothesis that the low cholinergic tone during SWS is necessary for the replay of new memories in the hippocampus and their long-term storage in neocortical networks. However, this low tone should not affect nondeclarative memory systems.
In this study, increasing central nervous cholinergic activation during SWS-rich sleep ... completely blocked SWS-related consolidation of declarative memories for word pairs in human subjects. The treatment did not interfere with consolidation of a nondeclarative mirror tracing task. Also, physostigmine did not alter memory consolidation during waking, when the endogenous central nervous cholinergic tone is maximal. To take advantage of this mechanism, one might experiment with taking all of one's DMAE shortly before bed. And again, if you do decide to take DMAE, make sure you take it away from ALCAR, TMG, choline, and other quaternary amines, as they compete for absorption at the BBB and in the GI.
To your health!
AOR
Haubrich DR, Gerber NH, Pflueger AB. Deanol affects choline metabolism in peripheral tissues of mice. J Neurochem. 1981 Aug;37(2):476-82.
Estrada C, Bready J, Berliner J, Cancilla PA. Choline uptake by cerebral capillary endothelial cells in culture. J Neurochem. 1990 May;54(5):1467-73.
Millington WR, McCall AL, Wurtman RJ. Deanol acetamidobenzoate inhibits the blood brain barrier transport of choline. Ann Neurol. 1978;4:302-306.
Rosen MA, Jones RM, Yano Y, Budinger TF. Carbon-11 choline: synthesis, purification, and brain uptake inhibition by 2-dimethylaminoethanol. J Nucl Med. 1985 Dec;26(12):1424-8.
