Dopamine D1 PAM

ASP4345 is an experimental oral drug from Astellas, a positive allosteric modulator of the dopamine D1 receptor: it does not switch the receptor on, but makes it respond to lower concentrations of dopamine. It was developed for the cognitive impairment of schizophrenia. Phase 1 found once-daily pharmacokinetics, entry into the cerebrospinal fluid and, in 48 patients over 14 days, faster reaction times than placebo on two computerised tests. The phase 2 trial then failed: in 233 patients, 50 or 150 mg a day for 12 weeks did no better than placebo on a standard cognitive battery or on a test of everyday functioning, and development was stopped. Those results are posted on the trial registry, which lists no journal publication of them.