Antiaggregatory activity of N-methyl- and N-isobutyl-1,2-diphenyl ethanolamines in rat platelets.
The ability of N-methyl-1,2-diphenyl ethanolamine (compound M), N-isobutyl-1,2-diphenyl ethanolamine (compound E), diltiazem and verapamil to inhibit in vitro ADP-induced platelet aggregation was examined in rat platelet-rich plasma. Pretreatment of the platelets with the compounds (0.1-3 mM) for 3 min at 37 degrees C, inhibited an ADP-induced aggregation in a concentration-dependent manner. The maximum percentage inhibitions induced by compounds M, E, diltiazem and verapamil were: 95.5 +/- 6.5, 98.4 +/- 7.5, 100 and 95.9 +/- 8.3% at concentrations of 3, 0.64, 0.96 and 0.4 mM, respectively (n = 8 - 12). The inhibitory dose 50 (ID50) values for compounds M, E, diltiazem and verapamil were 1.3 +/- 0.13, 0.29 +/- 0.01, 0.44 +/- 0.03 and 0.2 +/- 0.01 mM, respectively. The antiaggregatory effects were not antagonized by methylene blue (50-200 microM), but were completely antagonized (greater than 95%) by elevation of the Ca2+ level in the platelet-rich plasma by 0.2-0.7 mM. Co-administration of (-)propranolol (17 microM) with anyone of the compounds enhanced the antiaggregatory effects. The compounds (0.1-0.2 mM) enhanced the prostacyclin (0.01 nM)-induced antiaggregatory activity. The antiaggregatory effects of the compounds are likely to be due to an inhibition of influx of Ca2+ into the platelets.
el Tahir
K E
KE
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
el-Naser
M A
MA
Ageel
A M
AM
el-Obeid
H A
HA
al-Rashood
K A
KA
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008751:Methylene Blue / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004983:Ethanolamines; D010975:Platelet Aggregation Inhibitors; C069015:N-isobutyl-1,2-diphenylethanolamine; C069013:N-methyl-1,2-diphenylethanolamine; D000244:Adenosine Diphosphate; D011433:Propranolol; D014700:Verapamil; D011464:Epoprostenol; D004110:Diltiazem; D002122:Calcium Chloride; D008751:Methylene Blue