ASP 4345 is a novel in class dopamine D1 receptor PAM developed by Astellas Pharma. Unlike direct D1 agonists( see The Degradation Drug for why they are a bad idea ), binds to an allosteric site and potentiates the receptor’s response to endogenous dopamine, meaning a ceiling effect tied to dopamine tone instead of producing tonic receptor activation.
The primary indication was cognitive impairment associated with schizophrenia (CIAS), which remains an unmet need: no drug has FDA approval for this symptom cluster despite it being arguably more disabling than positive symptoms.
Desai et al. (2021) — “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.” Neuropsychopharmacology 46(6):1145–1151. PMID: 33203954 | DOI: 10.1038/s41386-020-00908-0
Desai et al. (2021) — “Pharmacokinetics of ASP4345 from Single Ascending-Dose and Multiple Ascending-Dose Phase I Studies.” Clinical Pharmacokinetics 60(1):79–88. PMID: 32533536 | DOI: 10.1007/s40262-020-00911-0