Kv3 channel modulators
Experimental medicines meant to support the fast-firing inhibitory nerve cells that are weakened in schizophrenia. Tested only in one small early study.
At a glance
- Type
- Medicine: potassium channel (Kv3.1 and Kv3.2) modulators
- Used for
- Tested in recent-onset schizophrenia in one early study
- Status
- Experimental, no trial in schizophrenia under way
- Evidence
- EarlyHow evidence is rated
- Administration
- By mouth. In the study, for 28 days alongside antipsychotics
- Common side effects
- Headache, drowsiness, abdominal pain, nausea
- In Europe
- Tested at King's College London. Not available outside research
Clinical summaryFor health professionals
- AUT00206 enhances Kv3.1 and Kv3.2 channels, which let parvalbumin interneurons fire fast and generate gamma rhythms.
- Phase 1b (King's College London): 24 men with recent-onset schizophrenia, 16 on AUT00206 and 8 on placebo, 28 days. No significant change in dopamine synthesis capacity; within the AUT00206 group, falls in dopamine synthesis tracked falls in symptoms (Angelescu 2022).
- Basmisanil (GABA-A α5 negative modulator; 213 patients, 24 weeks) and MK-0777 (GABA-A α2/α3 partial agonist; 60 patients) did not improve cognition (Umbricht 2026; Buchanan 2011).
What they are
In schizophrenia, a type of inhibitory nerve cell that contains the protein parvalbumin makes less GABA, the brain’s main dampening messenger. These cells fire very fast and set the rhythm of brain activity that working memory depends on.1 They rely on potassium channels called Kv3.1 and Kv3.2 to fire that fast. Kv3 channel modulators strengthen these channels, aiming to restore the cells’ function.2 How these cells fit into schizophrenia is explained in Beyond dopamine (opens in a new tab).
How well they work
The only study in patients so far, at King’s College London, gave the modulator AUT00206 or a placebo for 28 days to 24 men with recent-onset schizophrenia. Dopamine production in the striatum did not change overall, but in the men taking AUT00206, those whose dopamine production fell more had a larger fall in symptoms.3 The medicine also changed brain rhythms in the front of the brain and increased activity in the brain’s reward areas.2,4
AUT00206 is now being developed for Fragile X syndrome; for schizophrenia, its maker is studying related compounds in the laboratory.5
Two other medicines aimed at the inhibitory system did not improve thinking in schizophrenia: basmisanil, in 213 people over 24 weeks, and MK-0777, in 60 people.6,7
Side effects
In healthy volunteers, AUT00206 caused headache, drowsiness, abdominal pain and nausea.8
What we don’t know yet
- Whether strengthening these inhibitory cells improves symptoms or thinking in people with schizophrenia.
