Platelet activating factor (
PAF-acether) is a potential mediator of
asthma and
inflammation. Recently, the suggestion was made that inhibition of
PAF-acether by
disodium cromoglycate (DSCG) might be partly responsible for the effectiveness of DSCG in
asthma. We have extended these studies and examined the effects of
antiallergic and
bronchodilator drugs on
PAF-acether induced
bronchospasm after i.v. administration in guinea pigs and in vitro platelet aggregation in rabbits. Neither DSCG nor
Wy-41,195, a potent orally effective
antiallergic, altered either of the
PAF-acether responses. Furthermore, aerosolized
ipratropium,
promethazine,
ketotifen and
FPL 55712 failed to affect the
PAF-acether-induced
bronchospasm. The same drugs were also ineffective against platelet aggregation induced by
PAF-acether. In contrast, aerosolized
thiazinamium chloride inhibited the
bronchospasm and also inhibited
PAF-acether-induced platelet aggregation.
Thiazinamium chloride possessed weak antiaggregatory effects against
ADP and was without effect against
arachidonic acid-induced platelet aggregation. Both
lipoxygenase and
cyclooxygenase products of
arachidonic acid metabolism appear to be involved in
PAF-acether bronchospasm since i.v. administered
lipoxygenase inhibitors (
phenidone,
BW755c and NDGA) and
indomethacin independently inhibited this in vivo response. However, these drugs failed to alter platelet aggregation to
PAF-acether.
Thiazinamium chloride may be capable of directly antagonizing the
PAF-acether-induced platelet aggregatory response and, in addition, inhibiting the synthesis and/or effects of bronchoconstrictor
amines and endogenously generated
arachidonic acid metabolites.