Levomethadyl acetate (LAAM) is a synthetic opioid agonist with actions qualitatively similar to morphine (a prototypic mu agonist) and affecting the central nervous system (CNS) and smooth muscle. Principal actions include analgesia and sedation. Tolerance to these effects develops with repeated use. An abstinence syndrome generally occurs upon cessation of chronic administration similar to that observed with other opiates, but with slower onset, more prolonged course, and less severe symptoms. LAAM exerts its clinical effects in the treatment of opiate abuse through two mechanisms. First, LAAM cross-substitutes for opiates of the morphinetype, suppressing symptoms of withdrawal in opiate-dependent individuals. Second, chronic oral administration of LAAM can produce sufficient tolerance to block the subjective “high” of usual doses of parenterally administered opiates. Since the introduction of levomethadyl in 1995, the manufacturer has received increasing reports of severe cardiac-related adverse events, including QT interval prolongation, Torsades de Pointes and cardiac arrest. Other cardiac-related adverse events have also been reported, including arrhythmias, syncope, and angina. These events led to the removal of levomethadyl from the European market in March 2001. A very small number of patients may benefit from levomethadyl, but the risk of continued distribution and use no longer outweighs the overall benefits.

Lenperone (AHR 2277), or 4’-fluoro-4 [4-(p-fluorobenzoyl) piperidino] butyrophenone hydrochloride, is an antipsychotic compound which has been shown in preliminary experiments to possess those features essential for neuroleptic activity. Dopamine antagonist.

Propanidid (Epontol) is an analgetically potent and shortterm anesthetic, widely used in the 1960s. It was originally introduced by Bayer in 1963. Epontol, an injectable emulsion formulation of propanidid, provided by Bayer, was withdrawn from the market in Great Britain in 1983 because of concern over anaphylactoid reactions. Thus, in spite of the fact that propanidid provides shorter and more predictable recovery times than propofol, it has not been accepted widely as an injectable anesthetic. Even though Cremophor EL has been shown to cause anaphylactic reactions in humans in several cases (both when given intravenously and orally), it is still debated whether or not propanidid itself may have contributed to the reactions. It has been argued that the toxic effects or reactions to propanidid (and Althesin) were due to the drugs themselves. Several cases of negative reactions have been recorded for different drugs using Cremophor EL as solubilizer. This suggest that the negative reactions were mainly caused by Cremophor and not by the drug substances themselves. Propanidid is presumed to work as a GABA receptor agonist.

Lazabemide is a reversible and selective inhibitor of monoamine oxidase B (MAO-B) that was under clinical development against Parkinson's disease, Alzheimer's disease and as an aid to smoking cessation. The development of the drug was discontinued due to liver toxicity.

Beta-methyl digoxin (beta-methyl digoxin; Metildigoxin (INN, or medigoxin BAN, or methyldigoxin) is a methyl derivative (methyl group in position 4 of the digitoxose residue) of digoxin is a cardiac glycoside, a type of drug that can be used in the treatment of congestive heart failure and cardiac arrhythmia (irregular heartbeat). The substance is closely related to digoxin; it differs from the latter only by an O-methyl group on the terminal monosaccharide.

TIANEPTINE, a tricyclic antidepressant, is a drug used for the treatment of the major depressive disorder. It was discovered by The French Society of Medical Research in the 1980s. Unlike other tricyclic antidepressants, TIANEPTINE is a selective serotonin reuptake enhancer with minimal effects on norepinephrine and dopamine uptake. Also, it is a full agonist at the mu-opioid and delta-opioid receptors with no effect at the kappa-opioid receptors. Selective mu-opioid agonists typically induce euphoria, which may contribute to TIANEPTINE's antidepressant effect. It is marketed as Coaxil/Stablon in many European countries, but it is not available in the US.

Pipofezine (Azafen or Azaphen) is a tricyclic antidepressant (TCA) approved in Russia for the treatment of depression. It was introduced in the late 1960s and is still used today. Pipofezine has been shown to act as a potent inhibitor of the reuptake of serotonin. In addition to its antidepressant action, pipofezine has sedative effects as well, suggesting antihistamine activity. Other properties such as anticholinergic or antiadrenergic actions are less clear but are likely. The main advantage of Azafen compared with other tricyclic antidepressants is that this drug has a low toxic effect on the body, including the heart, and it does not block cholinergic receptors and does not change the activity of monoamine oxidase. The maximum concentration in the blood is reached after 1-2 hours after taking the drug. Absorbed in the gastrointestinal tract, metabolism occurs in the liver, and is excreted by Azaphene kidneys.

Ciramadol is an opioid agonist-antagonist analgesic with low potential for dependency. Ciramadol appears to be an effective analgesic, with tolerable gastrointestinal central nervous system side effects at both the 30-and 90-mg dose levels. Ciramadol is a mixed agonist-antagonist for the μ-opioid receptor. Side effects might include nausea and vomiting.

Medazepam is a benzodiazepine drug with anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. It is known by the following brand names: Azepamid, Nobrium, Tranquirax (mixed with bevonium), Rudotel, Raporan, Ansilan and Mezapam. Marketed in Russia. Indicated for the treatment of neurotic disorders and states, accompanied with sense of fear, anxiety, intension, raised irritability, insomnia, vegetative lability.

Fotemustine is a novel chloroethylnitrosourea alkylating agent approved for use in the treatment of metastasizing melanoma and Recurrent Malignant Gliomas. The antitumor activity of fotemustine is related to its ability to alkylate DNA. It's in vitro or in vivo pharmacological activity is similar or greater than that of other nitrosoureas. Significant activity has been found in mice xenograft models of human primary cerebral tumors after fotemustine intraperitoneal administration. Fotemustine has been registered for use in two indications: disseminated malignant melanoma, including cerebral metastases, and primary brain tumors. Fotemustine is currently used in Europe, particularly in France and Italy, as a salvage therapy for recurrent malignant gliomas. Myelosuppression, leucopenia, and thrombocytopenia are the most frequent side effects of treatment with fotemustine. The objective response to this treatment is between 26% and 70%, and the reported median survival time is 10 months. New drug combinations containing fotemustine and angiogenesis inhibitors, such as bevacizumab, are currently under development.