ASP‑4345
Dopamine D1 receptor positive allosteric modulator, an experimental agent for schizophrenia cognition.
Pharmacology
Contents
WHAT IS ASP-4345?
Detailed overview
ASP-4345 (ASP4345) is a dopamine D1 receptor positive allosteric modulator (PAM) developed by Astellas and investigated as an add-on treatment for the cognitive impairment associated with schizophrenia. Unlike classical D1 agonists it does not directly activate the receptor; instead it binds a secondary site and amplifies the brain's own dopamine response, targeting prefrontal cortex D1 signaling in order to avoid the cardiovascular and seizure risks typical of direct agonists. Phase 1 studies used once-daily oral dosing; the most common adverse effects were headache and somnolence, generally mild, and cognitive tests showed improvement. Development was discontinued after Phase 2; the compound is not an approved medicine and is not a dietary supplement.
Mechanism
Dopamine D1 receptor PAM (allosteric)
Half-life
~9-27 h (once-daily dosing)
Legal status
Investigational (halted at Phase 2)
Receptor profile
- Dopamine D1 receptorModerate
- Prefrontal cognitive circuitsWeak
- Auditory information processingWeak
Safety
Side effects, stop signs, contraindications
Side effects · 4
- Headache, the most common and typically mild adverse effect in trials
- Somnolence (drowsiness), mostly mild in severity
- Limited human safety database: only Phase 1 and Phase 2 studies were run, in small patient numbers
- Long-term safety is unknown because development was halted at Phase 2
Contraindications · 3
- Not an approved medicine: not authorized for human use, studied only in a research context
- Pregnancy and breastfeeding: safety not established, avoid
- In trials it was given as add-on to antipsychotics in schizophrenia; there is no data for standalone unsupervised use
Related Nootropics
Same therapeutic category
Studies
Related research and clinical findings
Phase 1 randomized study on the safety, tolerability, and pharmacodynamic cognitive and electrophysiological effects of a dopamine D1 receptor positive allosteric modulator in patients with schizophrenia
Desai A, Benner L, Wu R, et al.
Pharmacokinetics of ASP4345 from Single Ascending-Dose and Multiple Ascending-Dose Phase I Studies
Desai A, Benner L, Wu R, et al.
FAQ
FAQ
Dopamine D1 receptor positive allosteric modulator, an experimental agent for schizophrenia cognition.
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Structure & chemistry
The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.