Chapter 7: Deanol, A Test Case for Anti-Aging Drugs
Considering the present situation with antiaging drugs, we know that no such drug will get anything close to proof of effectiveness until years after we ourselves have reached old age, and many of us have died. I discussed this problem in the Introduction. It tells us that if we want to optimally prolong our lives, we should seriously consider taking one of these drugs NOW. This book reviews the available drugs with this purpose in mind.
A decision to take any unproven drug requires personal care, more so than taking standard prescription drugs. People differ in the degree of personal care they're willing to put into such choices. Some longevists simply take everything they can, forgetting about possible interactions. Some will take nothing stronger than a bit of Vitamin E. For my own personal choice, I have set three criteria which a drug must meet before I will consider it at all: There must be a substantial case that prolonged intake of the drug will not cause harm at dosages which will be theoretically effective on aging. The drug must have been shown to increase lifespan of some MAMMAL in a controlled experiment. The drug must be obtainable without great expense or a need to manufacture it ourselves.
These three criteria narrow the field very considerably. Although it's never been as noticed or as popular as drugs such as GH-3, BHT, or Vitamin E, there is another drug, deanol, which actually seems to me to pass all of these tests. Deanol was formerly available under several trade names: Deaner, Atrol, ANP-235, and Lucidryl. It has been used clinicially in psychiatry for over 15 years; dosage for aging and dosage for psychiatry would seem to be quite close (see below). Many people have already taken deanol for prolonged periods. The incidence of side effects is reported as low: the chief side effects are headache and muscle cramps. The only contraindication is a history of grand mal epilepsy. Lucidryl, when it was sold, was available on prescription only. If anything, the availability of deanol has improved since then: a salt of deanol, deanol bitartrate is now on sale in many health food stores, with no prescription required. (The contraindications discovered when it was on sale formally as a drug remain important for anyone who might consider taking deanol). Deanol was withdrawn from the market in the United States not because of any problems with toxicity, but simply because there came to be better drugs --- for the FDA approved purpose for which it was sold. This process should also tell us that FDA approval of a
drug for some use other than aging should not be relied on by anyone who wants to take any drug longterm! For its actions in aging, its relative obscur- ity, and its actions for other problems, deanol gives us a good test case.
The three papers by R. Hochschild in the bibliography list three published experiments in which lifespan increases were obtained with mice. Denham Harman reports a fourth experiment, and K. Nandy a fifth, to me by letters written in reply to my inquiries to them. Table I shows the dosages given and the lifespan increases obtained (see above).
The experiments are listed in order of dosage. The last column P is the statistical significance: these correspond to probabilities of 96.1%,
- 2%, and 92.3%, that the lifespan increases were not a result of chance. It's also noteworthy that the lowest dose gave the largest lifespan increase.
K. Nandy reports an experiment in which meclofenoxate (dimethylaminoethyl p-chlorophenoxyacetate, also called centrophenoxine), a closely related drug, was fed to mice. When dissolved in water, meclofenoxate breaks apart into deanol and p-chlorophenoxyacetic acid. Centrophenoxine is about 1/3rd deanol.
Nandy fed his mice 100 mg/klg of meclofenoxate (equal to 33mg/kg of deanol) per day for 30 months; at the end of the experiment 8 percent of controls, compared to 40 percent of the treated mice, remained alive. Denham Harman has tested meclofenoxate also at higher doses. Harman fed two groups of mice mexlofenoxate at dosages of 0.25 and 0.50 percent by weight of diet. His controls had an average life expectancy of 16.53 months with a standard deviation of 5.54 months; the animals on 0.25 percent meclofenoxate had a
life expectancy of 16.00 months with a standard deviation of 6.33 months; the
- 50 percent mice had a life expectancy of 10.64 months with a standard deviation of 4.64 months. Please note that at Harman's dosages he got a DECREASE in mean lifespan compared to controls.
Since Harman does not report the weight of his mice or the weight of food comsumed daily, it is hard to compare his results with those of Nandy and Hochschild. I have asked several people who work with experimental animals; they confirm a statement made in Nandy's letter that mice eat about 10 percent of their weight daily, and weigh an average of 30 gm. Using these figures to calculate a dosage in mg/kg for Harman's mice, we obtain a dosage of 250 mg/kg of meclofenoxate for the mice receiving 0.25 percent/weight and 500 mg/kg meclofenozate for the mice receiving 0.50 percent/weight. In terms of content of deanol these are dosages of 83 mg/kg deanol and 166 mg/kg deanol respectively.
The article by Pfeiffer allows us to find data on even higher doses of deanol. Pfeiffer reports giving mice dosages of 300 mg/kg to 500 mg/kg daily for periods of 3 months. On these doses the mice showed high emotionality, had seizures periodically, and showed a lower threshold for several convulsant drugs (half that of the controls). The oral LD50 for deanol tartrate is 3100 mg/kg on acute administration. The article by Pfeiffer also gives a very thorough discussion of other work on toxicity, much too extensive to report here; in particular it reports several other studies, lasting 3 or more months, of chronic toxicity. Pfeiffer originally invented Deaner and advocated its use for a long time afterwards.
The different results of the experiments of Hochschild, Harman, and Nandy may be explained in at least two ways. First, all of these experiments used widely varing dosages. Secondly, the strain of mouse may influence the effect of the different drugs : in Harman's experiments on antioxidants, some mice show large increases, others increases which are much smaller. I have reported the results of these experiments here; my personal opinion is that the decreases obtained by Harman happened almost certainly because Harman's dosages were too high.
What dose will affect aging in man?
Someone wishing to take deanol regularly for its possible influence on aging must first estimate a proper dosage to take. I shall discuss information bearing on this question; please note that at present there is no purely theoretical means of estimating proper dosage for human beings from dosage on mice. I discuss some of the issues involved in this problem in Appendix
The standard therapeutic dose reported in the clinical studies of deanol lies between 50 and 75 mg daily; I have found one clinical study which reports giving patients deanol at doses 1500 mg daily for periods as long as two years. None of these clinical studies report significant levels of toxicity. To estimate an effective dose for aging in humans we must resort to theory. The article by Bushby reports that the ED50 (Effective Dose) for drugs increases, in general, at a rate proportional to We, where W is the body weight of the animal and the exponent e lies between 2/3 and 1. Using Hochschild's lowest dose, I therefore obtain an estimate for human dose lying between 34 mg/day and 400 mg/day for a 60 kg man. Hochschild's second dose (20 mg/kg) gives an estimate between 100 mg/day and 1200 mg/day.
For comparison purposes I shall also estimate some dose equivalences to the dosages of Harman. If we suppose that the toxic effects increase also with the 2/3rd power of W, I obtain that a dose of 400 mg/day will have the same effects as Harman's dose of 0.25 percent/weight and a dose of 800 mg/kg day will have the same effects as Harman's dose of 0.50 percent/weight: in the latter case, a marked decrease in lifespan. These dosages give UPPER BOUNDS on the dosages which we would want to take.
Since the exponent e may exceed 2/3, we might reasonably take more than the minimum which might be effective (34 mg/day). It seems to me that a dosage of 100 mg/day would very likely be safe, and would have the advantage of allowing a margin in case the exponent were greater than 2/3.
I have also written Hochschild seeking his ideas on how dosage might be estimated for humans from his work on mice. In his reply he informed me that the US FDA had given him approval to conduct an experiment on human subjects, and that the dosage which he felt most inclined to try first was 200 mg/day. He suggested an upper bound of safety of 300 mg/day. The FDA approval would suggest that at least the FDA believes that such an experiment would be safe at 200 mg/day.
One further comment has great bearing on the question of dosage. Anyone who contemplates taking deanol is not in the position of making a final choice which fixes his dosage for all future time. He may easily resolve to watch very closely while work on this drug, and others, proceeds, and in response to any new information which may arise he can then change his choice of dosage, change to a different drug, or discontinue taking any drugs. Since deanol must be taken chronically over a long period to have effect on aging, and especially since the lifespans of mice are very short compared to our own, we may expect that further information will arise long before we have lived out our own lives. (This feature of drugs which may increase lifespan remains true for ANY such drug).
How to arrange to take deanol.
Riker Laboratories, the manufacturer of Deaner (deanol acetaminobenzoate) has withdrawn this drug from the market, not because of any problems with toxicity but because of a consensus by psychiatrists that other drugs worked better than Deaner for its marketed purpose. (Riker marketed Deaner for hyperactivity in schoolchildren). It therefore cannot be easily purchased as such. Since Hochschild used exactly this form of deanol in his experiments, it's possible that this form of deanol has significantly more effectiveness against aging than other forms. The Mexican company Bracco de Mexico continues to make and sell Lucidryl in Mexico, where users may buy it and bring it across the border quite legally.
Finally, many vitamin and health food companies still sell a closely related form of this drug, deanol bitartrate. I have not found any special reason why Riker chose its particular version of deanol, or any experiments suggesting that our bodies would absorb Riker's form (deanol aminobenzoate) better than others. While it's quite true that drug companies make small variations on standard drugs or even nondrug substances, just so they can patent and sell them, that fact alone does NOT tell us that Riker Laboratories did that in the case of Deaner. We must reserve judgement.
TO LEARN MORE: A review article done in 1959 containing much information on deanol, especially toxicity.
CC Pfeiffer "Parasympathetic neurohumors: possible precursors and effect on behavior" in INTERNATIONAL REVIEW OF NEUROBIOLOGY (1959), p. 195 Some clinical studies of deanol.
LJ Levine, "2-dimethylaminoethanol bitartrate in depressive illnesses and chronic schizophrenia" LANCET Sept 17, 1960, p. 653
M Shackleton et al "The use of DMAE in behavior states" MED J AUST. v2, 1962, pp. 337-339
E Miller, "Dimethylanminoethanol in the treatment of blepharospasm", NEW ENGLAND JOUR OF MED 289(13)(1973) 697 Papers reporting lifespan increases obtained with deanol.
R Hochschild, "Effect of dimethylaminoethyl p-chlorophenoxyacetate on the lifespan of male Swiss Webster albino mice" EXPERIMENTAL GERONTOLOGY 8(4) 1973, pp. 177-183
R Hochschild "Effects of various drugs on longevity in female C57BL/6J mice" GERONTOLOGIA 19(1973) pp. 271-280
R Hochschild "Effect of dimethylaminoethanol on the lifespan of senile male A/J mice", ibid, pp. 185-191 An article on the problems of assessing dosage and toxicity for one animal species from data on another.
SRN Bushby "Toxicity in chemotherapy", in RJ Schnitzer, F Hawking EXPERIMENTAL CHEMOTHERAPY, Vol I, Academic Press, NY, 1963
|This article contains chapters from the book, A GUIDE TO ANTIAGING DRUGS, published by PERIASTRON. |
Dr. Donaldson aimed to provide, in the GUIDE, a discussion of both the good points and the bad points, of every drug shown by experiment to prolong the healthy lifespan of some mammal. The mammals involved must normally reach at least the average lifespan of their species.
This Web Site provides only samples of only part of the GUIDE, which discusses other drugs also.