Bromantane

Bromantane, sold under the brand name Ladasten, is an atypical central nervous system (CNS) stimulant and anxiolytic drug of the adamantane family that is related to amantadine and memantine.

Although the effects of bromantane have been determined to be dependent on the dopaminergic and possibly serotonergic neurotransmitter systems, its exact mechanism of action is unknown,[3][4] and is distinct in its properties relative to typical stimulants such as amphetamine.

[10] Bromantane has been found to lower the levels of pro-inflammatory cytokines IL-6, IL-17 and IL-4 and to normalize behavior in animal models of depression, and may possess clinical efficacy as an antidepressant.

[18] A selection of quoted excerpts from the medical literature detail the differences between bromantane and typical stimulants:[10][9][16] Bromantane is well tolerated and elicits few side effects (including peripheral sympathomimetic effects and hyperstimulation), does not appear to produce tolerance or dependence, has not been associated with withdrawal symptoms upon discontinuation, and displays an absence of addiction potential, contrary to typical stimulants.

[23][24][25] Researchers discovered that amantadine and memantine bind to and act as agonists of the σ1 receptor (Ki = 7.44 μM and 2.60 μM, respectively) and that activation of the σ1 receptor is involved in the central dopaminergic effects of amantadine at therapeutically relevant concentrations; the authors of the study stated that this could also be the mechanism of action of bromantane, as it is in the same family of structurally related compounds and evidence suggests a role of dopamine in its effects.

[3][16][26] While bromantane can inhibit the reuptake of serotonin, dopamine, and to a lesser extent norepinephrine in vitro in rat brain tissue, the concentrations required to do so are extremely high (50–500 μM) and likely not clinically relevant.

[39] Amantadine was then developed and introduced for the treatment of Parkinson's disease due to its ability to increase dopamine levels in the brain.

[40] With the knowledge of the dopaminergic stimulant effects of the adamantane derivatives, bromantane, which is 2-(4-bromophenylamino) adamantane, was developed in the 1980s at the Zakusov State Institute of Pharmacology, USSR Academy of Medical Sciences (now the Russian Academy of Medical Sciences) in Moscow as "a drug having psychoactivating and adaptogen properties under complicated conditions (hypoxia, high environmental temperature, physical overfatigue, emotional stress, etc.)".

[10] The drug was notably given to soldiers in the Soviet and Russian militaries to "shorten recovery times after strong physical exertion".

[10] After the break-up of the Soviet Union in 1991, bromantane continued to be researched and characterized but was mainly limited in use to sports medicine (for instance, to enhance athletic performance).

[43] It demonstrated effectiveness and safety for the treatment of the condition in extensive, large-scale clinical trials,[7] and was approved for this indication in Russia under the brand name Ladasten sometime around 2009.