Inhibition of blood platelet functions by cationic amphiphilic drugs in relation to their physico-chemical properties.
The effects of bromadryl, dithiaden, chloroquine and propranolol on thrombin-stimulated rat platelet aggregation (measured turbidimetrically) and thromboxane B2 generation (detected by an RIA method) were compared with four selected physico-chemical parameters of these drugs. Platelet aggregation was inhibited in the rank order of potency: bromadryl > dithiaden > propranolol > chloroquine, which corresponded with the decrease in the net charge of the terminal methyl-(or ethyl-) groups in the side chain and with the increase of the dipole moment of drug molecules. On the other hand, the rank order of potency in which the drugs tested inhibited thromboxane B2 formation (chloroquine > dithiaden > bromadryl > propranolol) correlated well with the decline in molar refractivity of the drugs. No relationship was found between inhibitory effects of drugs and their partition coefficients. The results presented indicate that inhibition of platelet functions might consist of several types of drug-cell interactions, depend on the structure and physico-chemical properties of the drugs and cannot be estimated simply on the basis of partition coefficients.
Jancinová
V
V
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovak Republic. exfavega@savba.savba.sk
Májeková
M
M
Nosál
R
R
Petríková
M
M
D000818:Animals; D001582:Benzothiepins / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002738:Chloroquine / Q000494:pharmacology*; D004155:Diphenhydramine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010979:Platelet Function Tests; D011433:Propranolol / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D012984:Software; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis
D001582:Benzothiepins; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; C100170:dithiadene; D002738:Chloroquine; D004155:Diphenhydramine; D011433:Propranolol; D013917:Thrombin; C005715:embramine