Prostanoid mediated effects of centchroman, a non-steroidal oral contraceptive

Abstract

The effect of centchroman, a non-steroidal oral contraceptive, has been studied on platelet aggregation and on the products of arachidonate metabolism. Centchroman inhibited platelet aggregation in vitro and ex vivo after acute as well as chronic treatment for one year in laboratory animals. It did not affect aggregation of platelets in women taking centchroman for one year. It is an inhibitor of platelet cyclooxygenase as indicated by the inhibition of malonaldehyde and thromboxane B2 but has no effect on vascular cyclooxygenase activity ex vivo or at low concentration in vitro. Thus, centchroman is a safe antifertility agent without risk of thrombotic episodes associated with hormonal oral contraceptives.

Centchroman, a selective estrogen receptor modulator, as a contraceptive and for the management of hormone‐related clinical disorders

“…Lack of effect of centchroman on vascular cycloxygenase even up to 80 mg/kg dose ex vivo in rats or at low concentration (10 À5 M), effective in inhibiting malonaldehyde synthesis in vitro, suggests sparing effect of centchroman, which might prove bene®cial against risk of thrombotic episodes by shift of balance towards more bene®cial antiaggregatory PGI 2 . 194 Centchroman (1.25 mg/kg, po) administered for 5 consecutive days to immature female rhesus monkeys produces no signi®cant effect on thyroid weight, 134 I-uptake, conversion ratio or excretion rate of 24-hr urinary 17-OH-ketosteroids. 39 No effect has also been observed on 24 hr urinary 17ketosteroids in normospermic men (n 3; 32±40 years) receiving centchroman in increasing doses of 30, 60, and 120 mg/day (2 weeks/dose) for 6 weeks, but decreased 17-ketogenic steroids in all cases.…”

“…It does not cause hyperaggregability of platelets in women (n 11) using 30-mg weekly dose of centchroman for 1 year. 8,31,194 Its antiaggregatory effect appears to be due to inhibition of platelet cycloxygenase, 193,194 as evidenced by inhibition in malonaldehyde and thromboxane-B 2 synthesis. Lack of effect of centchroman on vascular cycloxygenase even up to 80 mg/kg dose ex vivo in rats or at low concentration (10 À5 M), effective in inhibiting malonaldehyde synthesis in vitro, suggests sparing effect of centchroman, which might prove bene®cial against risk of thrombotic episodes by shift of balance towards more bene®cial antiaggregatory PGI 2 .…”

Synthetic strategies in curcumin chemistry focused on anticancer applications

“…Among its molecular targets are transcription factors, growth factors and their receptors, cytokines, enzymes, and genes regulating cell proliferation and apoptosis. Extensive investigation suggests that curcumin has therapeutic potential in the treatment of various disorders (Scheme 1) as it is known to reduce blood cholesterol, [80][81][82][83][84][85] prevent low-density lipoprotein oxidation, [86][87][88] inhibit platelet aggregation, 89,90 suppress thrombosis 91,92 and myocardial infarction, [93][94][95][96] suppress symptoms associated with type II diabetes, [97][98][99][100][101][102][103][104] rheumatoid arthritis, [105][106][107][108][109] multiple sclerosis 110 and Alzheimer's disease, [111][112][113][114][115] inhibits HIV replication, [116][117][118][119][120][121][122][123][124] enhance wound heali...…”

Development and validation of a rapid, sensitive liquid chromatography–tandem mass spectrometry method using electrospray ionization for quantitation of centchroman in rat plasma and its application to preclinical pharmacokinetic study

“…which justifies its unusually long half-life but inter-individual variability has been found to exist [6]. Its pharmacokinetic interactions with several co-administered drugs have been studied in Sprague-Dawley rats and drug has been found safe for long term uses [2,7,8].…”