Direclidine
Switches on the M4 acetylcholine receptor alone, without a second drug to ease side effects. In phase 3 trials, including in Bulgaria, Hungary and Romania.
At a glance
- Type
- Medicine: M4 muscarinic receptor agonist
- Used for
- Tested in adults with acute schizophrenia
- Status
- In trials, in phase 3, including in Europe
- Evidence
- EarlyHow evidence is rated
- Administration
- Tablets, once a day
- Common side effects
- Sleepiness, dizziness, headache
- In Europe
- In phase 3 trials in Bulgaria, Hungary and Romania, as well as Serbia and the United States
Clinical summaryFor health professionals
- Selective M4 orthosteric agonist; licensed from Nxera Pharma (Neurocrine).
- Phase 2 (210 inpatients, 6 weeks): 20 mg once daily, PANSS 18.2 points down, 7.5 points better than placebo. Higher doses (40 mg, 60 mg, 30 mg twice daily) did not differ significantly from placebo (Neurocrine 2025).
- Phase 3 programme from 2025: acute trials of about 280 patients and a relapse-prevention trial; EU sites in Bulgaria, Hungary and Romania.
What it is
Direclidine switches on M4, one of the muscarinic receptors for acetylcholine. Unlike xanomeline–trospium (opens in a new tab), it acts on M4 alone and is taken without a second drug to block side effects elsewhere in the body.1 Its maker, Neurocrine Biosciences, licensed it from Nxera Pharma.2
How well it works
In a six-week phase 2 trial, 210 adults in hospital with a worsening of schizophrenia took one of four doses or a placebo. On the lowest dose, symptoms fell by 18.2 points, 7.5 points more than on placebo; the higher doses did not differ clearly from placebo.1 The results have not yet been published in a journal.
Phase 3 trials started in 2025. They include trials in acute illness and a trial of relapse prevention.1,3,4 In the European Union, one of them is recruiting in Bulgaria, Hungary and Romania.5
Side effects
In the phase 2 trial, the most frequent side effects were sleepiness, dizziness and headache. Digestive and heart-related side effects were uncommon, and weight did not increase more than on placebo.1
What we don’t know yet
- Why the lowest dose worked better than higher ones, and which dose the phase 3 trials confirm.
