Amineptine (7-[(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)amino]heptanoic acid) is available as either the free base (CAS 57574-09-1) or as the hydrochloride salt (CAS 30272-08-3). There are no chiral carbon atoms, therefore, no stereoisomers or racemates are possible.
Similarity to known substances and effects on the central nervous system
Amineptine is a synthetic, atypical tricyclic antidepressant with central nervous system stimulating effects. It is an indirect dopamine agonist, selectively inhibiting dopamine uptake and inducing dopamine release, with additional stimulation of the adrenergic system. Its antidepressant effects are similar to other tricyclic antidepressant drugs but it has a more rapid action, is better tolerated and has little cardiovascular, analgesic or anorectic effects. It produces a similar spectrum of pharmacological effects to psychomotor stimulants in Schedule II of the 1971 Convention on Psychotropic Substances.
There have been few animal studies regarding the dependence or abuse potential of amineptine. However, some clinical studies indicated that amineptine has both dependence and abuse potential, particularly in patients with a previous history of substance abuse. Clinical observations of significant abuse and dependence are reported in patients treated with amineptine in France. Its dependence potential appeared to be associated with its psychomotor stimulant effect. Withdrawal has been clinically manifested by anxiety, insomnia, psychomotor agitation or bulimia. Instances of dependence have been reported in Europe and Asia.
Actual abuse and/or evidence of likelihood of abuse
Amineptine abuse has mainly been reported in Europe and Asia. It has been withdrawn from the market in France, where the drug was developed a few decades ago, for reasons of considerable hepatotoxicity and abuse. Despite this measure, medical use in developing countries, as well as abuse still continues. The abuse-related adverse drug reaction reports for amineptine collected by the international drug monitoring programme indicate a larger number of case reports of abuse and dependence than anorectic stimulants currently placed in Schedule IV of the 1971 Convention on Psychotropic Substances, such as amfepramone. Response of governments to the WHO questionnaire also indicated limited diversion and abuse of the drug. Some reported hospital admissions due to adverse consequences of amineptine abuse.
The therapeutic usefulness of amineptine is low because of hepatotoxicity, secondary features such as acne eruption and anxiety and the availability of safer antidepressants. Of the 103 countries that responded to the WHO questionnaire, only 17 indicated amineptine use.
Given its significant hepatotoxicity, the degree of risk to public health and society associated with the abuse liability of amineptine is assessed to be substantial. Its therapeutic usefulness is rated to be from little to moderate, at best. Despite its withdrawal from the market in several countries, amineptine continues to be available in a number of countries. The likelihood of its abuse therefore warrants its placement under international control. On the basis of the above, it is recommended that amineptine be placed in Schedule II of the 1971 Convention on Psychotropic Substances.