Adjudin
Encyclopedia
Adjudin is a drug
which is under development as a potential non-hormonal male contraceptive
drug, which acts by blocking the production of sperm
in the testes, but without affecting testosterone
production. It is an analogue of the chemotherapy drug lonidamine
, an indazole-carboxylic acid, and further studies continue to be conducted into this family of drugs as possible contraceptives.
, adjudin was in phase II human trials.
As shown in mature male rats, the agent induces reversible germ cell
loss from the seminiferous epithelium by disrupting cell adhesion function between Sertoli and germ cells. It weakens the adhesion between the Sertoli cell
and maturing sperm
leading to a sloughing and loss of the latter. As it does not affect spermatogonia themselves the loss of fertility is reversible. In experiments hormonal levels (FSH
, LH
, testosterone
) were undisturbed during administration, and normal spermatogenesis
returned in 95% of the tubules of rats at 210 days after the drug had been discontinued.
When taken orally, the drug has very low bioavailability
. The oral dose effective for contraception is so high that there have been side effects in the muscles and liver. Coupling an Adjudin molecule to a mutant form of follicle-stimulating hormone
may solve this problem. The mutant FSH is modified such that it no longer induces Inhibin B production, but the membrane-bound FSH receptors on Sertoli cells still bind to it, delivering the Adjudin directly to the target cells. The adjudin-FSH can be either injected, delivered in an implant, or as a gel.
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
which is under development as a potential non-hormonal male contraceptive
Male contraceptive
Male contraceptives include condoms, withdrawal , and vasectomy. In other animals, castration is commonly used for contraception...
drug, which acts by blocking the production of sperm
Sperm
The term sperm is derived from the Greek word sperma and refers to the male reproductive cells. In the types of sexual reproduction known as anisogamy and oogamy, there is a marked difference in the size of the gametes with the smaller one being termed the "male" or sperm cell...
in the testes, but without affecting testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
production. It is an analogue of the chemotherapy drug lonidamine
Lonidamine
Lonidamine is a derivative of indazole-3-carboxylic acid, which for a long time, has been known to inhibit aerobic glycolysis in cancer cells. It seems to enhance aerobic glycolysis in normal cells, but suppress glycolysis in cancer cells. This is most likely through the inhibition of the...
, an indazole-carboxylic acid, and further studies continue to be conducted into this family of drugs as possible contraceptives.
, adjudin was in phase II human trials.
As shown in mature male rats, the agent induces reversible germ cell
Germ cell
A germ cell is any biological cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate near the gut of an embryo and migrate to the developing gonads. There, they undergo cell division of two types, mitosis and meiosis, followed by...
loss from the seminiferous epithelium by disrupting cell adhesion function between Sertoli and germ cells. It weakens the adhesion between the Sertoli cell
Sertoli cell
A Sertoli cell is a 'nurse' cell of the testes that is part of a seminiferous tubule.It is activated by follicle-stimulating hormone and has FSH-receptor on its membranes.-Functions:...
and maturing sperm
Spermatozoon
A spermatozoon is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote...
leading to a sloughing and loss of the latter. As it does not affect spermatogonia themselves the loss of fertility is reversible. In experiments hormonal levels (FSH
FSH
FSH may refer to:* Follicle-stimulating hormone* Fox Sports Houston, a regional Fox Sports Net affiliate station for the Houston, Texas area* Facioscapulohumeral muscular dystrophy* International Civil Aviation Organisation code for Flash Airlines...
, LH
Luteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
, testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
) were undisturbed during administration, and normal spermatogenesis
Spermatogenesis
Spermatogenesis is the process by which male primary germ cells undergo division, and produce a number of cells termed spermatogonia, from which the primary spermatocytes are derived. Each primary spermatocyte divides into two secondary spermatocytes, and each secondary spermatocyte into two...
returned in 95% of the tubules of rats at 210 days after the drug had been discontinued.
When taken orally, the drug has very low bioavailability
Bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
. The oral dose effective for contraception is so high that there have been side effects in the muscles and liver. Coupling an Adjudin molecule to a mutant form of follicle-stimulating hormone
Follicle-stimulating hormone
Follicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
may solve this problem. The mutant FSH is modified such that it no longer induces Inhibin B production, but the membrane-bound FSH receptors on Sertoli cells still bind to it, delivering the Adjudin directly to the target cells. The adjudin-FSH can be either injected, delivered in an implant, or as a gel.
External links
- "Trials for alternative male Pill show no side-effects" at the Independent
- "Sperm-stopping male pill hope" at BBC News
- Adjudin (a Lonidamine analogue) at MaleContraceptives.org