VU0448088 (ML253) is a potent positive allosteric modulator of the tricyclic muscarinic acetylcholine receptor subtype 4 (M4) and can cross the blood-brain barrier. It exhibits EC50 values of 56 nM and 176 nM in humans and rats, respectively. The compound VU0448088 holds potential for use in psychiatric research.

mAChR4:56 nM (EC50)

VU0448088 was administered intraperitoneally (i.p.) at dosages of 3, 10, 30, 56.6, and 100 mg/kg, and demonstrated a dose-dependent reversal of amphetamine-induced hyperlocomotion in rats. Specifically, at a dose of 10 mg/kg, a modest reduction of 26% in hyperactivity was observed. Notably, at the higher doses of 30, 56.6, and 100 mg/kg, there were significant reductions in hyperactivity, recorded at 47.9%, 53.7%, and 57.3%, respectively.