| Popis: |
About three decades ago a new era in the control of fertility began with the discovery of the steroidal hormonal contraceptive drugs, including estradiol and progesterone. The oral administration of progesterone inhibited ovulation in women, but heavy bleeding had to be controlled by estrogen. The development of a combination of pills dates back to Inhoffen in Germany, who synthesized ethisterone and ethinyl estradiol. Djerassi synthesized 19-norprogesterone and norethindrone, which were more potent than the naturally occurring progesterone. Subsequently, a large number of steroidal contraceptives were developed, of which, the fluorinated derivatives, 21-fluoroprogesterone (1a) and 21-fluoro-17alpha-acetoxyprogesterone (1b) were 2 to 4 times as active as progesterone; 21-fluoro-6alpha, 16alpha-dimethyl-17alpha-acetoxyprogesterone (1c) was 20 times as active as ethisterone. The effort to overcome heavy bleeding led to the synthesis of non-steroidal antifertility agents; aliphatic and allied derivatives; alicyclic compounds; aromatic and condensed systems; and heterocycles. All possible types of non-steroidal potential antifertility agents are reviewed, covering literature up to Chemical Abstracts (C.A.) volume 115 (1991), with occasional C.A. volume 116 (1992) references. A large number of prostaglandins and their derivatives were found to be useful as contraceptives even in mammals. Cloprosterol induced estrus in murrah and swamp buffalos. The prostaglandins El an PGF2alpha, when injected into rats, decreased sperm count and suppressed sperm motility and fertility. A number of prostaglandins were synthesized for evaluation of biological activity. Fluoroprostaglandins were evaluated for the interruption of pregnancy in hamsters (80-90 g body weight). Gossypol and gossypol acetate showed a high degree of antifertility activity in male and female animals up to mammals. Indomethacin administered up to 4 hours following mating decreased the number of implantations and increased premature resorption and mortality in rats; administered 8 hours after mating, it decreased pregnancies by 40%. |
