DL-Phenylalanine

TRADE NAMES

DL-Phen-500 (Key Company), DL-PA-500 (Bio-Tech Pharmacal), Endorphenyl (Tyson Neutraceuticals).

DESCRIPTION

DL-phenylalanine refers to a racemic mixture consisting of 50% D-phenylalanine and 50% L-phenylalanine. L-phenylalanine is an essential protein amino acid. (See L-Phenylalanine.) D-phenylalanine is the enantiomer of L-phenylalanine. D-phenylalanine is a nonprotein amino acid, meaning that it does not participate in protein biosynthesis. D-phenylalanine and other D-amino acids are, however, found in proteins, in small amounts, particularly aged proteins and food proteins that have been processed. The biological functions of D-amino acids remain unclear. Some D-amino acids, such as D-phenylalanine, may have pharmacologic activity.

DL-phenylalanine is marketed as a nutritional supplement for its putative analgesic and antidepressant activities. D-phenylalanine is not available as a nutritional supplement.

ACTIONS AND PHARMACOLOGY

DL-phenylalanine has putative analgesic and antidepressant activities.

MECHANISM OF ACTION

The putative analgesic activity of DL-phenylalanine may be explained by the possible blockage by D-phenylalanine of enkephalin degradation by the enzyme carboxypeptidase A.

The mechanism of DL-phenylalanine's putative antidepressant activity may be accounted for by the precursor role of L-phenylalanine in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects.

PHARMACOKINETICS

See L-Phenylalanine for the pharmacokinetics of this amino acid. D-phenylalanine is absorbed from the small intestine, following ingestion, and transported to the liver via the portal circulation. A fraction of D-phenylalanine appears to be converted to L-phenylalanine. D-phenylalanine is distributed to the various tissues of the body via the systemic circulation. D-phenylalanine appears to cross the blood-brain barrier with less efficiency than L-phenylalanine. A fraction of an ingested dose of D-phenylalanine is excreted in the urine. There is much about the pharmacokinetics in humans that is unknown.

INDICATIONS AND USAGE

There is very preliminary evidence that DL-phenylalanine might be helpful in some with depression. It may also have some analgesic properties. It has not shown benefit in the treatment of attention deficit disorder.

RESEARCH SUMMARY

In a small open trial, depressed subjects were treated with 75 to 200 mg of DL-phenylalanine daily for 20 days. Significant benefit was reported. The same researchers subsequently conducted a double-blind study in which depressed patients were given either 150 to 200 mg of DL-phenylalanine or 150 to 200 mg of imipramine daily for 30 days. There was no significant difference in the antidepressant activity of the two substances. Both of these studies are dated. There are a few studies showing that D-phenylalanine, not available as a supplement, has some analgesic effects. Thus, DL-phenylalanine, an equal mixture of D-phenylalanine and L-phenylalanine, may have some of the same activity, although this has not been persuasively demonstrated to date.

CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS

CONTRAINDICATIONS

DL-phenylalanine is contraindicated in those with phenylketonuria. It is also contraindicated in those taking non-selective monoamine oxidase (MAO) inhibitors. DL-phenylalanine is contraindicated in those hypersensi- tive to any component of a DL-phenylalanine-containing supplement.

PRECAUTIONS

Pregnant women and nursing mothers should avoid supplementation with DL-phenylalanine.

Tardive dyskinesia has been reported to be exacerbated after ingestion of L-phenylalanine by schizophrenics. Therefore, those with schizophrenia should exercise extreme caution in the use of DL-phenylalanine.

Those with hypertension should exercise caution in the use of DL-phenylalanine.

ADVERSE REACTIONS

L-phenylalanine will exacerbate symptoms of phenylketonuria if used by phenylketonurics. L-phenylalanine was reported to exacerbate tardive dyskinesia when used by some with schizophrenia.

INTERACTIONS

DRUGS

Non-selective monoamine oxidase (MAO) inhibitors: including phenelzine sulfate, tranylcypromine sulfate and pargyline HCl — Concomitant use of L-phenylalanine and non-selective MAO inhibitors may cause hypertension.

Selegiline: L-phenylalanine and the selective MAO inhibitor selegiline may have synergistic antidepressant activity if used concomitantly.

Neuroleptic drugs: L-phenylalanine may potentiate the tardive dyskinesia side effects of neuroleptic drugs if used concomitantly.

OVERDOSAGE

No reports of overdosage.

DOSAGE AND ADMINISTRATION

Those who use DL-phenylalanine supplements typically use 375 mg to 2.25 grams daily.

HOW SUPPLIED

Capsules — 200 mg, 500 mg, 600 mg

Powder

Tablets — 500 mg

LITERATURE

Beckman H, Athen D, Olteanu M, Zimmer R. DL-phenylalanine versus imipramine: a double-blind controlled study. Arch Psychiatr Nervenkr. 1979; 227:49-58.

Beckman H, Ludolph E. [DL-phenylalanine as an antidepressant. Open study.] [Article in German.] Arzneimittelforschung. 1978; 28:1283-1284.

Beckman H, Strauss MA, Ludolph E. DL-phenylalanine in depressed patients: an open study. J Neural Transm. 1977; 41:123-134.

Dove B, Morgenstern E, Gores E. [Analgesic effect, tolerance development and dependence potential of D-phenylalanine.] [Article in German.] Pharmazie. 1985; 40:648-650.

Ehrenpreis S. Pharmacology of enkephalinase inhibitors: animal and human studies. Acupunct Electrother Res. 1985; 10:203-208.

Halpern LM, Dong WK. D-phenylalanine: a putative enkephalinase inhibitor studied in a primate acute pain model. Pain. 1986; 24:223-237.

Lehmann WD, Theobald N, Fischer R, Heinrich HC. Stereospecificity of phenylalanine plasma kinetics and hydroxylation in man following oral application of a stable isotope-labeled pseudo-racemic mixture of L- and D-phenylalanine. Clin Chim Acta. 1983; 128:181-198.

Walsh NE, Ramamurthy S, Schoenfeld L, Hoffman J. Analgesic effectiveness of D-phenylalanine in chronic pain patients. Arch Phys Med Rehabil. 1986; 67:436-439.

Wood DR, Reimherr FW, Wender PH. Treatment of attention deficit disorder with DL-phenylalanine. Psychiatry Res. 1985; 16:21-26.