Ro 24-4736 is an effective and selective platelet-activating factor antagonist.

Ro 24-4736 competes with [3H]PAF for its receptor site on dog platelets (IC50: 9.8±1.0 nM). Ro 24-4736 selectively inhibits PAF-induced aggregation of guinea pig, dog, and human platelets with concentration dependence [1].

Ro 24-4736, a new platelet-activating factor (PAF) antagonist, stands out for its exceptional oral (p.o.) potency, bioavailability, and duration of action compared to other evaluated PAF antagonists in a guinea pig model. Despite demonstrating no inhibitory effect on the bronchoconstrictor actions of leukotriene D4 or histamine, Ro 24-4736 effectively counters PAF-induced in vivo bronchoconstriction and ex vivo platelet aggregation in a dose-dependent manner, highlighted by its ID50 values of 0.006 mg/kg (p.o.) for bronchoconstriction and 0.004 mg/kg (p.o.) for platelet aggregation, respectively. Notably, a single p.o. dose of 0.03 mg/kg ensures a complete blockade of PAF-induced platelet aggregation for up to 8 hours and sustains action against PAF for 30 hours in vivo, without affecting bronchoconstrictor responses to other agents even at high doses (up to 10 mg/kg). Further investigations reveal that orally administered Ro 24-4736 reduces airway hyper-reactivity triggered by inhaled antigens in sensitized guinea pigs without influencing bronchoalveolar leukocyte accumulation. Distribution studies using 14C-Ro 24-4736 in male rats show significant uptake by various organs, with peak concentrations reached within 5 minutes post-administration, except in the small intestine, abdominal fat, stomach, and large intestine (4 hours). By 48 hours post-dosing, only 3.5% of the drug remains in tissues, with 6.1% detected in the gastrointestinal tract's lumen.