Description
Methacycline is a tetracycline-class antibiotic that is active against a wide range of Gram-positive and Gram-negative organisms. It is readily absorbed from the gastrointestinal tract and reaches a maximum concentration at about the fourth hour, declining to a negligible amount in about 24 hours. It is more active than tetracycline against a number of bacteria.
Chemical Properties
yellow crystalline powder
Originator
Rondomycin ,Pfizer ,UK ,1963
Uses
A broad spectrum, anti bacterial, semisynthetic antibiotic related to Tetracycline
Uses
analgesic, narcotic antagonist
Uses
Methacycline hydrochloride is a salt prepared from methacycline taking advantage of the basic dimethylamino group which protonates and readily forms a salt in hydrochloric acid solutions. The hydrochloride is the preferred formulation for pharmaceutical applications. Like all tetracyclines, methacycline hydrochloride shows broad spectrum antibacterial and antiprotozoan activity and acts by binding to the 30S and 50S ribosomal subunits, blocking protein synthesis.
Uses
Broad spectrum, semisynthetic antibiotic related to Tetracycline. Antibacterial.
Definition
ChEBI: Methacycline hydrochloride is an organic molecular entity.
Manufacturing Process
To a stirred solution of 4.6 g (0.01 mol) of anhydrous oxytetracycline in 40 ml of dry tetrahydrofuran is added 3.5 g (0.021 mol) of pyridine-sulfur trioxide complex. After 16 hours of stirring at room temperature, the resulting suspension is filtered, and the solid is slurried with 25 ml of 2% hydrochloric acid for 10 minutes, filtered and thoroughly washed with methanol followed by ether. The pale yellow crystalline 5-oxytetracycline-6,12-hemiketal-12-sulfuric acid ester melts at 210°C.
500 mg 5-oxytetracycline-6,12-hemiketal-12-sulfuric acid ester, prepared as
described, is added to 4 ml dry liquid hydrogen fluoride, and the mixture is
stirred for 1.5 hours at ice bath temperature. The hydrogen fluoride is then
evaporated in a stream of nitrogen and the resulting gummy solids are
triturated with about 15 ml ether and filtered. The resulting solid hydrofluoride
salt is further purified by suspending in water, adjusting the pH to about 4,
and extracting the 6-methylene-5-oxytetracycline free base from the aqueous
phase with ethyl acetate. The extract is separated and evaporated to dryness
under reduced pressure. The resulting residue is triturated with ether and
filtered, and the solid is recrystallized from methanol-acetone-etherconcentrated hydrochloric acid to obtain the product as a purified
hydrochloride, according to US Patent 3,026,354.
brand name
Rondomycin (Medpointe).
Therapeutic Function
Antibiotic
General Description
The synthesis of methacycline, 6-deoxy-6-demethyl-6-methylene-5-oxytetracycline hydrochloride (Rondomycin), reportedby Blackwood et al. in 1961, was accomplished bychemical modification of oxytetracycline. It has an antibioticspectrum like that of the other tetracyclines but greater potency;about 600 mg of methacycline is equivalent to 1 g oftetracycline. Its particular value lies in its longer serum halflife;doses of 300 mg produce continuous serum antibacterialactivity for 12 hours. Its toxic manifestations and contraindicationsare similar to those of the other tetracyclines.
The greater stability of methacycline, both in vivo and invitro, results from modification at C-6. Removal of the 6-hydroxy group markedly increases the stability of ring C toboth acids and bases, preventing the formation of isotetracyclinesby bases. Anhydrotetracyclines still can form, however,by acid-catalyzed isomerization under strongly acidicconditions. Methacycline hydrochloride is a yellow to darkyellow, crystalline powder that is slightly soluble in waterand insoluble in nonpolar solvents. It should be stored intight, light-resistant containers in a cool place.
References
[1] E G HUBERT. Activity of methacycline, related tetracyclines, and other antibiotics against various L-forms and their parent bacteria in vitro.[J]. Antimicrobial Agents and Chemotherapy, 1972, 2 4: 276-280. DOI:
10.1128/aac.2.4.276[2] R S MORTON D W H. Methacycline (rondomycin) in gonorrhoea.[J]. The British Journal of Venereal Diseases, 1966, 42 3: 175-177. DOI:
10.1136/sti.42.3.175[3] DAVID G MCLONE. Gonorrheal urethritis in men treated with one oral dose of methacycline.[J]. Public health reports (Washington, D.C.: 1896), 1968, 83 1: 87-89.
