Anti-platelet activating factor, anti-leukotriene D4 and some other antiallergic activities of mequitazine.
The bronchoconstrictions of guinea pigs elicited in vivo by leukotriene D4 (LTD4) and platelet activating factor (PAF) were inhibited by pretreatment with mequitazine (CAS 29216-28-2) (p.o.) in a dose-dependent manner at doses of 5-20 mg/kg. Mequitazine (0.5-50 nmol/l) also inhibited LTD4- and PAF- induced contractions of guinea pig tracheal chain. These results suggest that mequitazine possesses antagonistic activity for LTs and PAF; the effects of mequitazine against these two agonists were much more potent than those of ketotifen. The histamine release induced by either of compound 48/80, concanavalin A or A23187 was inhibited by mequitazine at concentrations ranging from 1 to 20 mumols/l. In the inhibition process, mequitazine may act not only to inhibit the Ca2+ release from intracellular Ca store of mast cells but also to stabilize the lipid bilayer of the cell membrane as shown in the order parameter and hypotonic hemolysis. From the present study, it was assumed that mequitazine may exert antiallergic activity by antagonizing LTs and PAF as well as by inhibiting histamine release from mast cells.
Tasaka
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Akagi
M
M
Mio
M
M
Izushi
K
K
Aoki
I
I
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006168:Guinea Pigs; D006461:Hemolysis / Q000187:drug effects; D006636:Histamine Release / Q000187:drug effects; D006967:Hypersensitivity / Q000517:prevention & control*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects; D010640:Phenothiazines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000187:drug effects
D010640:Phenothiazines; D010972:Platelet Activating Factor; D013189:SRS-A; D015060:1,2-Dipalmitoylphosphatidylcholine; D000242:Cyclic AMP; D002118:Calcium; C006069:mequitazine