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 is markedly superior in terms of p.o. potency, bioavailability, and p.o. duration of action in comparison with other PAF antagonists evaluated in this guinea pig model. Ro 24-4736 is a new platelet-activating factor antagonist. Ro 24-4736 displays no inhibitory activity toward the bronchoconstrictor effects of leukotriene D4 or histamine. Ro 24-4736 dose-dependently inhibits in vivo bronchoconstriction (ID50: 0.006-mg/kg p.o.) and ex vivo platelet aggregation (ID50: 0.004 mg/kg; p.o.) induced by PAF in guinea pigs. Time course studies display a complete blockade of PAF-induced platelet aggregation (ex vivo) up to 8 hr after a single p.o. the dose of 0.03 mg/kg as well as a long duration of action in vivo (30 hr). The in vivo PAF antagonistic activity is specific because even at high p.o. doses (up to 10 mg/kg). Studies are also performed with Ro 24-4736 in additional in vivo models. When administered p.o. to sensitized guinea pigs, the drug attenuates inhaled antigen-induced airway hyper-reactivity without effect on bronchoalveolar lavage leukocyte accumulation. The tissue distribution of the 14C-label in male rats following a single intravenous dose of 1.0 mg/kg of 14C-Ro 24-4736 indicates appreciable uptake by the liver, kidney, heart, and gastrointestinal tract. Peak plasma and tissue concentrations are seen at 5 minutes after dosing except for the small intestine (4 hrs) and abdominal fat, stomach, and large intestine (4 hrs). At 48 hours, only 3.5% of the dose is present in the tissues, and 6.1% in the lumen of the gastrointestinal tracts [1][2].