Table 1.
Non-hormonal male contraception
| Drug | Target | Mechanism | Adverse Event | Clinical Trials |
|---|---|---|---|---|
| Testis | ||||
| Gossypol | Exact target unknown (presumed seminiferous tubules) | Inhibition of spermatogenesis and sperm motility through oxidative stress | Irreversible Infertility in up to 20%; Dose dependent hypokalemia |
Yes |
| Triptolide | Exact target unknown (presumed seminiferous tubules) | Unknown | Irreversible infertility | Yes |
| Indenopyridine enantiomers and derivatives (CDB 4022), l-CDB 4022, l-RTI-4587-073) | Exact target unknown (presumed Sertoli cell) | Unknown | Species dependent irreversible Infertility | No |
| Lonidamine Derivatives (H2-gamendazole and Adjudin) | Apical ectoplasmic specialization (Sertoli-Germ cell junction) | Disruption of Sertoli-Germ Cell Junction preventing sperm maturation | Liver Inflammation, Muscle Atrophy, Infertility. | No |
| JQ1 | Testis specific bromodomain | Impairs chromatin remodeling during spermatogenesis | None in mice | No |
| BMS 189453 | Retinoic Acid Receptor α, β g antagonist | Blocks spermatogonial differentiation | None noted at low doses. | No |
| BMS 189532 and 195614 | Retinoic Acid Receptor α antagonist | Blocks spermatogonial differentiation | None noted | No |
| WIN 18,446 (BDAD) | Aldehyde Dehydrogenase 1a2 (ALDH1a2) inhibitor preventing conversion of Retinaldehyde (vitamin A) to Retinoic Acid | Blocks spermatogonial differentiation through suppression of Stra8 expression | Impairs liver aldehyde dehydrogenase resulting in Disulfiram like reaction with alcohol | Yes |
| Epididymis | ||||
| None | HE6 (G protein coupled receptor) | Defect of reabsorption of testicular fluids in epididymal ductules | Unknown | No |
| None | CRISP-1 glycoprotein (secreted by epididymal epithelium) | Suppresses sperm capacitation and inhibits sperm-egg fusion in rats and mammals | Unknown | No |
| Sperm Motility and Sperm Egg Fusion | ||||
| None | EPPIN: epididymal protease inhibitor; | binding of semen coagulation protein (semenogelin 1) which impairs sperm motility | Unpredictable irreversible infertility; Variable immune response | No |
| N-Butyldeoxynojiri mycin (Miglustat) | Glycophospholipid Biosynthesis Inhibitor (mice only) | Impairs sperm motility | No effect on sperm in man; GI symptoms and Weight loss | Yes |
| HC-056456 | CatSpers: Ca permeable ion channels | Mutation or defect of CatSper genes prevent sperm hyperactivation/Reduced Sperm Motility | No other phenotype reported in knockout mice | No |
| S-3-chlorolactaldehyde | Glyceraldehyde-3-Phosphate dehydrogenase-S (Gapdhs): Sperm specific glycolysis (GAPD2 human specific homolog of GAPDS) | Inhibits sperm specific glycolysis | Many | No |