Bromantane

What it is

Bromantane, marketed under the brand name Ladasten in Russia, is a synthetic small molecule built around an adamantane ring, a rigid carbon-based structure also found in some antiviral drugs. It was developed at a Russian pharmacology institute and studied as an actoprotector, a term used mainly in Russian pharmacology research for a compound studied for sustaining physical and mental performance during demanding conditions such as heat or prolonged exertion.

Its proposed way of working is unusual among stimulant-type compounds. Rather than binding a receptor directly or blocking the reabsorption of a brain chemical, laboratory studies describe it as changing which genes are switched on in nerve cells, raising the activity of genes that make the enzymes needed to build dopamine and serotonin [2]. Reports also describe it lowering activity of the GABA transporter, a protein that normally clears GABA, a calming brain chemical, from the space between nerve cells.

How it is studied

The main human evidence is a large, multicenter clinical trial run across 28 centers in Russia, giving a daily oral amount for 28 days to patients diagnosed with a fatigue-related condition called asthenic disorder [1]. Separate laboratory work in rats has measured activity of the tyrosine hydroxylase gene, an early step in making dopamine, in specific brain regions after treatment, and a human pharmacology study has measured how the compound is absorbed and cleared from the body after a single oral administration.

What studies report

• In a trial of 728 patients with a fatigue-related diagnosis, 28 days of daily oral bromantane was linked to improvement in about three out of four patients on a standard clinician rating scale, with side effects reported in only about 3 percent of patients. [1]
• In rats, bromantane raised activity of the tyrosine hydroxylase gene, an early step in making dopamine, by roughly two to two and a half times in brain regions tied to motivation and movement. [2]
• In a human pharmacology study, a single oral administration was absorbed at a moderate rate, with roughly 42 percent reaching the bloodstream and clearing with a half-life of about eleven hours. [3]

What is not known

Nearly all of the clinical evidence for bromantane comes from Russian research groups using the specific asthenic-disorder diagnosis common in that country's medical practice, which does not map cleanly onto diagnostic categories used elsewhere. No large, independently run, placebo-controlled trial has been published outside Russia, and it is not established how the compound's effects would look in a different patient population or under different trial designs.

Reported adverse findings

• In the 728-patient Russian trial, about 3 percent of patients reported side effects, and less than 1 percent discontinued treatment because of them, a low rate as reported in that specific trial population. [1]

Regulatory status

Bromantane is approved in Russia, since 1997, for the treatment of asthenic disorders, a fatigue-related diagnosis. It is not approved by the FDA, the European Medicines Agency, or Health Canada for any use, and the World Anti-Doping Agency has banned it as a prohibited substance since 1997.