ABSTRACT
Antagonists of platelet activating factor (PAF) can be classified into three types: PAF analogues, natural products or their derivatives, and synthetic compounds. This chapter focuses on the preclinical and clinical pharmacology of the latter group of synthetic compounds: hetrazepines. When J. Casals-Stenzel started the screening for leads with PAF-antagonistic activity in 1982 he discovered that both the fonzotriazolo-diazepines, alprazolam and triazolam and the thieno-triazolo-diazepine brotizolam, inhibited PAF-induced platelet aggregation in vitro and furthermore that they were also active against PAF-effects in vivo. Once brotizolam had been discovered as a lead for a potent antagonist of PAF the requirement for a dissociation of the CNS-sedative effects from the retained PAF-antagonistic properties was evident. Antagonism of PAF-induced aggregation in platelet-rich plasma, whole blood, and washed platelets has been shown for WEB 2086 on platelets of different sources and species.
