Antiplatelet agents affecting the interaction of Tissue Factor-Factor VIIa complex with Factor X in a continuous-flow reactor.
The purpose of the present study was to examine the role of antithrombotic agents in the activation of Factor X in the presence of the Tissue Factor-Factor VIIa (TF-VIIa) complex in a continuous-flow reactor. Tissue Factor immobilized in a phospholipid bilayer on the inner surface of a capillary tube (internal diameter = 0.27 mm) was exposed to a perfusate containing Factors VIIa and X flowing at a flow rate of 12.7 microliters/min, corresponding to a wall shear rate of 100 s-1. Factor Xa (the activated form of Factor X) in the effluent was determined by a chromogenic assay. The effectiveness of two platelet aggregation inhibitors, alpha,alpha'-bis-[3-(N,N-diethylcarbamoyl)piperidino-p-xylene dihydrobromide (A-1) and alpha,alpha'-bis-[3-N-benzyl-N-methylcarbamoyl)piperidino]-p-xylen e dihydrobromide (A-4) in inhibiting Factor X activation is reported here. The results suggest that the Tissue Factor pathway, mediated through TF-VIIa complex, produces significantly lower levels of Factor Xa in the presence of compounds A-1 and A-4. On the basis of these findings, it appears that the anticoagulation action of these compounds reinforces their platelet aggregation-inhibitory properties. These carbamoylpiperidines (nipecotamides) therefore appear to be useful antithrombotic agents.
Gir
S
S
Department of Mechanical Engineering, University of Memphis, TN 38152, USA.
Reavis
R
R
Turitto
V T
VT
Gollamudi
R
R
D005069:Evaluation Studies as Topic; D015942:Factor VIIa / Q000737:chemistry*; D005170:Factor X / Q000737:chemistry; D005343:Fibrinolytic Agents / Q000737:chemistry*; D015394:Molecular Structure; D009557:Nipecotic Acids / Q000737:chemistry*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry*; D013925:Thromboplastin / Q000737:chemistry*
D005343:Fibrinolytic Agents; D009557:Nipecotic Acids; D010975:Platelet Aggregation Inhibitors; C043099:alpha, alpha'-bis(3-(N,N-diethylcarbamoyl)piperidino)-4-xylene; C077875:alpha,alpha'-bis(3-(N-benzyl-N-methylcarbamoyl)piperidinol)-4-xylene; D005170:Factor X; D013925:Thromboplastin; D015942:Factor VIIa