Myristicin, a natural product found in nutmeg oil and nutmeg extract, contains the carbon skeleton for a series of drugs of abuse related to the 3,4-methylenedioxyamphetamines (MDAs). Myristicin, 1-(3-methoxy-4,5-methylenedioxyphenyl)-2-propene, was identified as the major component of commercially available nutmeg oil and in the organic extract of nutmeg powder. Myristicin, or methoxysafrole, is a benzodioxole with slight MAO-inhibiting properties. Myristicin is active at the 5-HT receptors in the brain, and has been shown to have hypotensive, sedative, anti-depressant, anesthetic, hallucinogenic, and serotonergic properties. Large doses generally cause hyper-excitability, followed by CNS depression. Myristicin has been shown to have potent anti-cancer properties. A 65% inhibition of the tumor multiplicity in the lung of rats was observed as the result of treatment of myristicin in rats. Myristicin showed a 31% inhibition of tumor formation in the forestomach of rats. Mice given 5 to 50 mg doses of myristicin, showed 4- to 14-fold increase in liver glutathione S-transferase (GST) activity.

Nomifensine was developed by Hoechst AG as a potent inhibitor of noradrenaline, dopamine, and 5-HT uptake displayed antidepressant activity. It was first marketed in the UK in 1977 for the treatment of depression. Between 1977 and 1982 there were reports of hemolytic anemia in association with the drug, and this suspected adverse reaction was included in the 1981 edition of the data Sheet Compendium. FDA published a notice of its determination that Merital capsules were removed from the market for safety reasons.

Phenylalanine is a biologically essential amino acid that acts as a precursor to tyrosine and the catecholamines (epinephrine, norepinephrine, dopamine, and tyramine), and is a constituent of many central nervous system neuropeptides. Normal dietary levels of phenylalanine are approximately 1-2 grams daily. Phenylalanine appears in two forms which are identical mirror images of each other: L-phenylalanine, a nutritional supplement, and D-phenylalanine, an effective painkiller and antidepressant due to its ability to inhibit the breakdown of enkephalins, the brain’s natural pain killers.

Tryptophan is alpha-aminoacid that is used in the biosynthesis of proteins. It is essential aminoacid in humans, meaning the body cannot synthesize and it must be obtained from the diet. Tryptophan is a precursor of serotonin, and as such is sold over the counter in many countries as a dietary supplement for use as an antidepressant, anxiolytic and sleep aid, however application of tryptophan in these indications is not approved by FDA.

Tybamate is a minor tranquilizer that is chemically and pharmacologically related to meprobamate. It is useful in treating anxiety and tension associated with psychoneurotic disorders.

Flurothyl (bis-2,2,2-trifluoroethyl ether) is a volatile convulsant acting as a GABAA antagonist that was extensively used historically to induce seizures in severely depressed patients as an alternative to electroconvulsive shock therapy. The main current use of flurothyl is in scientific research for inducing seizures in laboratory animals. Flurothyl is used to induce seizures in immature rats. Flurothyl is a potent and rapidly acting central nervous system stimulant that produces seizures within minutes of exposure. It has been previously demonstrated that flurothyl seizures during the first days and weeks of life in rats result in several morphological and behavioral changes. Mortality after acute flurothyl exposure is low.

ETRYPTAMINE (MONASE®), similar to the hallucinogenic tryptamines, is an inhibitor of monoamine oxidase, introduced for use as an antidepressant. It was withdrawn from the market due to problems with agranulocytosis and other side effects. However, it's activity is still under scientific investigation.

Nialamide is a non-selective, irreversible monoamine oxidase inhibitor of the hydrazine class. It was previously used as an antidepressant (trade name Niamid) but was withdrawn by Pfizer in 1963 due to the risk of hepatotoxicity.

Benactyzine, an anticholinergic drug, had been used as an antidepressant in the treatment of depression and associated anxiety. It is no longer used in medicine due to its ineffectiveness but is widely used in scientific research. Benactyzine is a muscarinic antagonist which also inhibits the nicotinic acetylcholine receptor.

Iproniazid is a non-selective, irreversible monoamine oxidase inhibitor (MAO) of the hydrazine class. It was originally developed for the treatment of Tuberculosis, but in 1952, its antidepressant properties were discovered when researchers noted that patients given isoniazid became inappropriately happy. Iproniazid is no longer clinically prescribed and has been withdrawn due to incidences of hepatotoxicity.