To study the mechanism whereby toxic doses of
methaqualone cause a
bleeding tendency in humans, the effects of
methaqualone,
diphenhydramine, and the combination of
methaqualone plus
diphenhydramine on blood platelet function were investigated. Exposure of human platelets in platelet-rich plasma in vitro to final concentrations of
methaqualone ranging from 1.1 to 4.5 X 10(-4)) M resulted in nearly complete inhibition of the secondary phase and significant inhibition of the primary phase of
adenosine diphosphate (
ADP)--induced aggregation. Both the slope and height of
collagen-induced aggregation responses were reduced significantly in vitro by the
drug. When
methaqualone final concentrations of 1.1, 2.3, and 4.5 X 10(-4) M were studied in the presence of
diphenhydramine (1.1, 2.3, and 4.5 X 10(-5) M, respectively), the degree of inhibition of
ADP-induced aggregation was only slightly greater (not significant) than that observed with
methaqualone. The platelets of rabbits injected intravenously with
methaqualone, 10 mg/kg, demonstrated a significantly decreased ability to aggregate with
ADP and
collagen 30 and 60 min after administration of the
drug. These results suggest that a
drug-induced defect of blood platelet function may play a role in the
bleeding associated with
methaqualone toxicity.