17-Methyltestosterone

Absorption

The methyl group aids to increase oral bioavailability.

Toxicity

Side effects include amnesia, anxiety, discolored hair, dizziness, dry skin, hirsutism, hostility, impaired urination, paresthesia, penis disorder, peripheral edema, sweating, and vasodilation.

Description

Methyltestosterone is a synthetic analog of testosterone that possesses all of the properties of testosterone, exhibiting stimulatory action on the development of male sex organs and secondary sex characteristics, although it is not degraded by enzymes in the gastrointestinal tract, and therefore it can only be taken orally

Chemical properties

white to slightly yellowish-white crystalline

Originator

Metandren ,Ciba,US,1941

The Uses of 17-Methyltestosterone

Androgen. It has been used as an androgenic agent. Controlled substance (anabolic steroid).

The Uses of 17-Methyltestosterone

It is used for the same indications as testosterone for sexual underdevelopment, functional problems of the reproductive system, and the vascular nerve disorders associated with climacteric problems in men. It is also used for dysfunctional uterine bleeding in premenopausal and menopausal women as well as for breast and ovarian cancer.

Indications

Methyltestosterone is an anabolic steroid hormone used to treat men with a testosterone deficiency. It is also used in women to treat breast cancer, breast pain, swelling due to pregnancy, and with the addition of estrogen it can treat symptoms of menopause.

Background

A synthetic anabolic steroid used for treating men with testosterone deficiency or similar androgen replacement therapies. Also, has antineoplastic properties and so has been used secondarily in women with advanced breast cancer. Methyltestosterone is a schedule III drug in the US.

Definition

ChEBI: A 17beta-hydroxy steroid that is testosterone bearing a methyl group at the 17alpha position.

Manufacturing Process

0.6 g of 17-Methyl-?5,6-androstenediol-(3,17) is heated under reflux cooling during 20 hours in 50 cm3 of benzene and 12 cm3 of acetone with 3 g of tertiary chloromagnesium butylate, which may be prepared by conversion of acetone with methyl magnesium chloride. The magnesium is then removed by shaking out with dilute H2SO4; the benzene layer is washed with water, dried with sodium sulfate and then evaporated to dryness. Methyltestosterone (MP 160° to 162°C) is obtained in a yield of more than 75% of the theory, according to US Patent 2,384,335.

brand name

Android (Valeant);Metandren (Novartis); Oreton (Schering); Testred (Valeant); Virilon (Star).

Therapeutic Function

Androgen

Pharmacokinetics

Testosterone is a steroid hormone from the androgen group. Testosterone is primarily secreted from the testes of males. In females, it is produced in the ovaries, adrenal glands and by conversion of adrostenedione in the periphery. It is the principal male sex hormone and an anabolic steroid. In both males and females, it plays key roles in health and well-being. Examples include enhanced libido, energy, immune function, and protection against osteoporosis. On average, the adult male body produces about twenty times the amount of testosterone than an adult female's body does.

Pharmacokinetics

The synthesis of 17α-methyltestosterone made available a compound that was orally active in daily doses between 10 and 50 mg, which is equivalent to a 400 mg oral dose of testosterone. The presence of a 17α alkyl group reduces susceptibility to hepatic oxidative metabolism, thereby increasing oral bioavailability by slowing metabolism. Following oral administration, methyltestosterone is well absorbed from the gastrointestinal tract, with a half-life of approximately 3 hours. This drug has the androgenic and anabolic activities of testosterone. Although orally active, it is more effective when administered sublingually. The alkylated oral androgens should be viewed as potentially hepatotoxic and should not be used.

Safety Profile

Poison by intraperitoneal route. Moderately toxic by ingestion. Human teratogenic effects by ingestion: developmental abnormalities of the urogenital system. Experimental teratogenic and reproductive effects. Human systemic effects: cholestatic jaundce, weight loss or decreased weight gain. Questionable human carcinogen producing liver tumors. A synthetic androgenic steroid. When heated to decomposition it emits acrid smoke and irritating fumes.

Synthesis

Methyltestosterone, 17|?-hydroxy-17|á-methylandrost-4-en-3-one (29.1.7), is also synthesized from androstenolone by reacting it with methylmagnesiumiodide, forming the corresponding tertiary alcohol (29.1.6), and subsequent oxidation of the hydroxyl group at C3 to a ketone using chromium (VI) oxide. Simultaneous isomerization of the double bond takes place under the reaction conditions, giving the desired methyltestosterone (29.1.7).

Metabolism

Hepatic. Testosterone is metabolized to 17-keto steroids through two different pathways. The major active metabolites are estradiol and dihydrotestosterone (DHT).

Purification Methods

This anabolic steroid is crystallised from hexane or hexane/*benzene. It has E1cm 1% 495-530 at 241nm (EtOH). The colour reaction with 2,4-dinitrophenyl hydrazine is used for assaying it. [Gornall & Macdonald J Biol Chem 201 279 1953.] In another colour reaction the sterone (1mg) in acetic acid (0.2ml) + 88% H3PO4 (2mL) is allowed to stand for 1hour when it becames fluorescent. After 1hour it is diluted with acetic acid (~3mL) and provides a strong yellow fluorescence with the intensity of 50-100 times that of estrone. [Stuart & Stuckey J Pharm Pharmacol 1 130 1949, Openauer Rec Trav Chim Pays-Bas 56 137 137, Beilstein 8 IV 1010.]