09 March 2009

Phenmetrazine (Filon, Preludin)

Pronunciation: fen-MET-rah-zeen
Chemical Abstracts Service Registry Number: 134-49-6
Formal Names: Filon, Preludin
Informal Names: Sweeties
Type: Stimulant (anorectic class).
Federal Schedule Listing: Schedule II (DEA no. 1631)
USA Availability: Prescription

Uses.
Immediately upon announcement of the drug’s discovery in 1954 it was utilized in Germany as an appetite suppressant. A couple years later the same medical use began in the United States with expansive claims about patients obtaining substantial weight loss without having to follow a regimen of dieting, claims that became more modest as experience with the drug spread. One experiment testing the drug’s influence on appetite yielded a result relevant to drug experiments in general: The substance worked better when people knew its intended effect. If people knew they were supposed to feel less hungry, they noticed less desire for food and then ate less. Early reports praised phenmetrazine for producing more appetite loss than amphetamine and with fewer unwanted effects. Since then phenmetrazine has fallen into disfavor due to concern about addictive potential even though the drug is described as resembling caffeine more than amphetamine.

In dogs phenmetrazine has only one sixth to one tenth the strength of amphetamine. One type of canine experiment showed dextroamphetamine to be 250 times stronger than phenmetrazine. In dogs a much higher dose of phenmetrazine is needed for the same weight loss produced by benzphetamine, and an experiment with 75 humans had results consistent with that tendency,
finding phenmetrazine to be less effective than benzphetamine in promoting weight loss. In contrast, another human weight reduction experiment with 81 persons was unable to demonstrate such a difference. That study did show, however, that users obtain fewer amphetamine effects from phenmetrazine than from dextroamphetamine.

Phenmetrazine has worked as an antidepressant, and for some overweight persons that effect may enhance the drug’s appeal (overeating can be a response to depression). The substance shows effectiveness against motion sickness and against symptoms of diabetes insipidus. As a possible cure for bedwetting, the drug produced mixed results. The compound has also been
used to treat asthma and Parkinson’s disease.

Drawbacks.
Intravenous abuse can harm muscles and kidneys. Phenmetrazine can produce standard amphetamine effects such as euphoria, restlessness, jumpiness, insomnia, tics, fatigue reduction, faster breathing, and higher blood pressure. Studies have found phenmetrazine’s actions on patients with heart trouble or hypertension (high blood pressure) to be measurable but negligible.

Taking the high blood pressure medicine propranolol along with phenmetrazine can relieve cardiac effects without diminishing anorectic effects. Studies with diabetic users find phenmetrazine having little influence on blood sugar levels or on insulin needs.

Fluctuating emotions and even psychosis have been attributed to phenmetrazine abuse. Psychosis can include hallucinations and paranoia. That affliction can stop when drug taking stops, or instead the drug may break down barriers releasing full-fledged and long-lasting schizophrenia. Phenmetrazine interferes with dreaming during sleep, which in itself may cause psychological trouble.

Abuse factors.
Tests of drug preference, in which users could choose among several substances, found benzphetamine and phenmetrazine to have about the same amount of appeal even though benzphetamine is a Schedule III substance (a status implying a lower addictive potential than phenmetrazine). In one such test, volunteers found phenmetrazine to be a satisfying substitute
for dextroamphetamine but preferred the latter. Abusers of amphetamine and methamphetamine have routinely switched to phenmetrazine when their favored drug was unavailable.

Drug interactions.
An experiment found that chlorpromazine (Thorazine) interacts with phenmetrazine, hindering phenmetrazine’s normal anorectic benefit.

Cancer.
In pregnant women phenmetrazine may undergo transformations suspected of promoting childhood tumors.

Pregnancy.
Phenmetrazine was formerly prescribed to pregnant women seeking to lose weight. A study of over 10,000 birth and childhood records found the drug having no “severe” impact on fetal development. Other studies have found no birth defects at all, although medical literature from the early 1960s does contain a handful of reports in which the drug is suspected of harming fetuses. Those suspicions were never verified but were strong enough to suspend medical use of the drug in some countries for a while.

Combination products.
Filon combines phenmetrazine theoclate (CAS RN 13931-75-4) and phenbutrazate hydrochloride and is promoted as having phenmetrazine’s weight loss characteristics while lacking hazard of addiction. Initial clinical trials showed Filon to be an effective anorectic with fewer of phenmetrazine’s unwanted qualities, but a later study found the two drugs
to have the same unwanted effects. A case of Filon addiction also surfaced, but that single instance hardly proves Filon to have more addictive potential than any other drug considered to have low or zero potential.

Additional scientific information may be found in:
Gilstrap, L.C. III, and B.B. Little, eds. Drugs and Pregnancy. New York: Elsevier, 1992.

Martin, W.R., et al. “Physiologic, Subjective, and Behavioral Effects of Amphetamine, Methamphetamine, Ephedrine, Phenmetrazine, and Methylphenidate in Man.”
Clinical Pharmacology and Therapeutics 12 (1971): 245–58.

Mellar, J., and L.E. Hollister. “Phenmetrazine: An Obsolete Problem Drug.” Clinical
Pharmacology and Therapeutics 32 (1982): 671–75.

Negulici, E., and D. Christodorescu. “Phenmetrazine Psychosis.” British Medical Journal
3 (1968): 316.

Penick, S.B, and J.R. Hinklele. “The Effect of Expectation on Response to Phenmetrazine.”
Psychosomatic Medicine 26 (1964): 369–73.

Rosen, A., and I.J. Oberman. “Addiction to Phenmetrazine Hydrochloride and Its Psychiatric
Implications.” Journal of the American Osteopathic Association 59 (1960): 722–26.

Spillane, J.P. “The Use of Phenmetrazine.” The Practitioner 185 (1960): 102–6.

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