Three Forgotten Anxiolytic Drugs
Research and education, not medical advice.
Anxiety is very common. Unfortunately, there are few drugs that are “pure” anxiolytics that do not also affect all sorts of other things (e.g., SSRIs). Benzodiazepines work great but they come with an addiction potential and are also terrible for long-term brain health – occasional use is fine though.
Various EU countries have their own drugs that are not used in other countries. For example, metamizole is a great analgesic drug that is mainly used in Austria and Germany, in which it is the most commonly prescribed analgesic. However, it is barely used in any other first world country and it is even banned in the US (which may have indirectly contributed to the opioid crisis). Similarly, some EU countries have their own anxiolytic drugs that are rarely found anywhere else.
#1 Etifoxine
Etifoxine is an anxiolytic drug mainly prescribed in France. It is thought to be an indirect GABAergic potentiator (vs. benzodiazepines who directly bind to the GABA-A receptor). It binds to mitochondrial translocator protein (TSPO), which leads to increased neurosteroid synthesis (such as allopregnanolone). These neurosteroids then potentiate GABA-A receptor activity, promoting relaxation and reducing anxiety. This is similar to zuranolone, which had been approved for postpartum depression. Zuranolone is an analogue of pregnanolone allosterically activating the GABA-A receptor.
#2 Opipramol
Opipramol is chemically a tricyclic substance but quite different from other tricyclics, similar to tianeptine and amineptine. Like other tricyclics, it is a quite dirty drug acting on multiple receptors. While it does slightly inhibit the H1 receptor (causing tiredness), its main mechanism seems to be acting on sigma1 and sigma2 receptors, which are implicated in all sorts of things. Sigma receptors are located in the endoplasmic reticulum (meaning their location is intracellular) where they play a key role in potentiating intracellular calcium mobilization. Clinically, it is used as an anxiolytic drug in Germany and other European countries.
#3 Fabomotizole
Fabomotizole is an anxiolytic drug mainly used in Russia. Its mechanism of action is poorly defined. It seems to be somehow GABAergic and sigma receptor agonism is thought to have some involvement, but nobody knows. All sorts of other mechanisms have been implicated such as melatonin receptor modulation and MAO-inhibition. Nonetheless, Russians have reportedly been using the drug successfully for over 20 years.
Thanks for reading. Repost from: https://desmolysium.substack.com/p/three-forgotten-anxiolytic-drugs
Archived into the Nootopics wiki from r/NooTopics — originally posted by u/makefriends420 on 2026-06-23. Curated, not authored by the community.
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