7115. Pentamidine

Nomenclature

CAS number: 100-33-4
4,4′-[1,5-Pentanediylbis(oxy)]bisbenzenecarboximidamide; 4,4′-(pentamethylenedioxy)dibenzamidine; 4,4′-diamidino-α,ω-diphenoxypentane.
C19H24N4O2; mol wt 340.42.
C 67.04%, H 7.11%, N 16.46%, O 9.40%.

Description and references

Prepn: A. J. Ewins, GB 507565 (1939); J. N. Ashley et al., J. Chem. Soc. 1942, 103; of isethionate: G. Newbery, A. P. T. Easson, US 2394003 (1946 to May & Baker). Trypanocidal activity: E. M. Lourie, W. Yorke, Ann. Trop. Med. Parasitol. 33, 289 (1939). Preliminary pharmacological studies in animals: R. Wien, ibid. 37, 1 (1943). Activity in fibrinolytic systems: J. D. Geratz, Thromb. Diath. Haemorrh. 29, 154 (1973). Pharmacodynamics in men and mice: T. P. Waalkes et al., Clin. Pharmacol. Ther. 11, 505 (1970). In vitro activity against Pneumocystis carinii: E. L. Pesanti, C. Cox, Infect. Immun. 34, 908 (1981). Uptake and distribution of aerosolized form in animals: R. J. Debs et al., Am. Rev. Respir. Dis. 135, 731 (1987). In vivo efficacy of aerosolized form in rats: eidem, Antimicrob. Agents Chemother. 31, 37 (1987). Determn in plasma, urine and tissues: T. P. Waalkes, V. T. DeVita, J. Lab. Clin. Med. 75, 871 (1970); by HPLC: C. M. Dickinson et al., J. Chromatogr. 345, 91 (1985). Preliminary clinical evaluation in P. carinii pneumonia: V. T. DeVita et al., N. Engl. J. Med. 280, 287 (1968). Comparison with sulfamethoxazole-trimethoprim mixture in P. carinii pneumonia in AIDS: J. M. Wharton et al., Ann. Intern. Med. 105, 37 (1986). Early review of pharmacology, mode of action and clinical applications: E. B. Schoenbach, E. M. Greenspan, Medicine 27, 327-377 (1948). Review: S. Drake et al., Clin. Pharm. 4, 507-516 (1985); M. Sands et al., Rev. Infect. Dis. 7, 625-634 (1985); of activity, pharmacokinetics and therapeutic use: K. L. Goa, D. M. Campoli-Richards, Drugs 33, 242-258 (1987).

Chemical structure

Properties

Crystallizes as colorless plates from water. Dec 186°.

Derivative

Dihydrochloride.

Nomenclature

CAS number: 50357-45-4
C19H24N4O2.2HCl; mol wt 413.34.
C 55.21%, H 6.34%, N 13.55%, O 7.74%, Cl 17.15%.

Properties

Fine needles from dil HCl, mp 232-234°. LD50 in mice (mg/g): 0.028 i.v.; 0.064 s.c. (Wein).

Derivative

Isethionate.

Nomenclature

CAS number: 140-64-7
M & B 800; RP-2512; NebuPent (Astellas); Pentacarinat (Sanofi-Aventis); Pentam (Astellas).
C19H24N4O2.2C2H6O4S.

Properties

Hygroscopic, very bitter crystals, mp ≈180°. Slight butyric odor. Sol in water (≈1 in 10 at 25°, ≈1 in 4 at 100°); sol in glycerol, more readily on warming; slightly sol in alcohol. Insol in ether, acetone, chloroform, liquid petr. pH of a 5% w/v soln in water: 4.5 to 6.5.

Derivative

Dimethanesulfonate.

Nomenclature

CAS number: 6823-79-6
Pentamidine mesylate.
C19H24N4O2.2CH3SO3H.

Properties

White powder.

Therapeutic Category

Antiprotozoal (Trypanosoma, Leishmania); antipneumocystic.

Therapeutic Category (Veterinary)

Antiprotozoal (Babesia, Leishmania).

Keywords

Antipneumocystic; Antiprotozoal (Leishmania); Antiprotozoal (Trypanosoma)