Effect of a PAF antagonist, BN52063, on PAF‐induced bronchoconstriction in normal subjects.

Abstract

1. The effects of an oral platelet activating factor (PAF) antagonist, BN52063, or matched placebo on inhaled PAF challenge were assessed in a double‐blind study in eight normal subjects. 2. PAF (24 micrograms) induced an immediate bronchoconstriction, with a maximum fall in flow at 30% of vital capacity from a partial flow volume manoeuvre (Vp30) of 47.1 +/‐ 7% (mean +/‐ s.e. mean) 5 min after inhalation following placebo treatment. Repeated PAF challenges at 15 min intervals resulted in tachyphylaxis of the bronchoconstrictor response. 3. Two hours after the ingestion of BN52063 (120 mg) the maximum bronchoconstriction induced by inhaled PAF was attenuated (35.9 +/‐ 9% fall at 5 min) with a significant reduction (P less than 0.05) in response after the first and second inhalations. 4. Inhaled PAF induced an immediate neutropenia (73.2 +/‐ 9% fall 5 min after inhalation) followed by a rebound neutrophilia, which were unaffected by pretreatment with BN52063. 5. Oral ingestion of a dose of BN52063 which is effective in reducing skin responses to PAF gave partial protection against the bronchoconstrictor effect of inhaled PAF in normal subjects.

Effects of a PAF‐antagonist (BN 52063) on bronchoconstriction and platelet activation during exercise induced asthma.

“…An increase in circulating 1-TG after antigen inhalation was not inhibited by aspirin or sulphinpyrazone indicating that the involvement of cyclooxygenase products is unlikely (Gresele et al, 1985). However in a recent study the increase in 3-TG and PF4 plasma concentrations following exercise challenge could be attenuated by pretreatment with salbutamol and sodium cromoglycate (Johnson et al, 1986), which have been shown to exert nonspecific inhibition of the effects of PAF (Baranes et al 1986;Basran et al 1982;Hellegouarch et al, 1988 (Chung et al, 1987;Roberts et al, 1988b), it has been suggested that inhalation of BN 52063 might be advantageous because of high local concentrations. Our data, however, show a worsening of pulmonary function after single dose inhalation, possibly due to local bronchial irritation.…”

“…Since 120 mg of BN 52063 p.o. exhibit only partial protection against the effects of cutaneous and inhaled PAF (Chung et al, 1987;Roberts et al, 1988b), it has been suggested that inhalation of BN 52063 might be advantageous because of high local concentrations. Our data, however, show a worsening of pulmonary function after single dose inhalation, possibly due to local bronchial irritation.…”

“…These include inhibition of platelet aggregation, bronchoconstriction, the late response and activation of eosinophils (Braquet et al, 1987). In human subjects BN 52063 given orally has been shown to inhibit the inflammatory response to subcutaneous injections of PAFacether (Chung et al, 1987;Guinot et al, 1986;Roberts et al, 1988a) and inhaled PAF (Roberts et al, 1988b). In vitro investigations have shown that bronchial effects of PAF can be potentiated by cooling of the bronchial preparations (Chand et al, 1986).…”

Enterocolitis necrotizante neonatal: Etiopatiogenia y prevención

“…El FAP actiia a (rave's de receptores celulares especificos y se han descrito varios antagonistas en ese nivel 51 , que pueden prevenir la Iesi6n intestinal que este factor induce eti ratas 23 . En Europa los antagonistas de FAP han sido probados en voluntaries adultos con asma 52 , pero no para prevenir la enterocolitis necrotizante en ninos recidn nacidos.…”

The role of histamine in the acute inflammatory responses to intradermal platelet activating factor.

“…PAF also produces degranulation and aggregation of platelets (Henson, 1970;Kuster et al, 1986); whilst in intact tissue it causes vasoconstriction (Humphrey et al, 1982), extravasation (Humphrey et al, 1982;Hwang et al, 1985), bronchoconstriction (Cuss et al, 1986;Roberts et al, 1988) and cellular accumulation (Archer et al, 1985a;Henocq & Vargaftig, 1988). Its importance flare weal atopic as a putative primary mediator in asthma is the subject of much current research interest.…”