5571. Loperamide
Nomenclature
CAS number: 53179-11-6
4-(4-Chlorophenyl)-4-hydroxy-N,N-dimethyl-α,α-diphenyl-1-piperidinebutanamide; 4-(p-chlorophenyl)-4-hydroxy-N,N-dimethyl-α,α-diphenyl-1-piperidinebutyramide. C29H33ClN2O2; mol wt 477.04.
C 73.01%, H 6.97%, Cl 7.43%, N 5.87%, O 6.71%.
Description and references
Prepn: Janssen et al., FR 2100711; eidem, US 3714159 (1972, 1973 to Janssen); Stokbroekx et al., J. Med. Chem. 16, 782 (1973). LC-MS/MS determn in plasma: B. Streel et al., J. Chromatogr. B 814, 263 (2005). Series of articles on pharmacology, toxicology, metabolism, and clinical studies: Arzneim.-Forsch. 24, 1640-1665 (1974). Toxicity studies: C. J. E. Niemegeers et al., ibid. 1633, 1636. Review: D. A. Shriver et al., in Pharmacological and Biochemical Properties of Drug Substances vol. 3, M. E. Goldberg, Ed. (Am. Pharm. Assoc., Washington, DC, 1981) pp 461-476. Comprehensive description: J. Van Rompay, J. E. Carter, Anal. Profiles Drug Subs. 19, 341-365 (1990).
Derivative
Hydrochloride.Nomenclature
CAS number: 34552-83-5
PJ-185; R-18553; Arret (Janssen); Blox (Biomed. Foscama); Brek (Irbi); Dissenten (SPA); Fortasec (Esteve); Imodium (Janssen); Imosec (Janssen); Imossel (Janssen-Solucal); Lopemid (Gentili); Lopemin (Dainippon); Loperyl (Zambeletti); Suprasec (J & J); Tebloc (Dukron). C29H33ClN2O2.HCl; mol wt 513.50.
C 67.83%, H 6.67%, Cl 13.81%, N 5.46%, O 6.23%.
Properties
Crystals from isopropanol, mp 222-223°. uv max (0.1N HCl/2-propanol, 10/90 v/v): 253, 259, 265, 273 nm (ε 532, 648, 581, 233). Soly (g/100ml): water (pH 1.7) 0.14; citrate-phosphate (pH 6.1) 0.008; citrate-phosphate (pH 7.9) <0.001; methanol 28.6; ethanol 5.37; 2-propanol 1.11; dichloromethane 35.1; acetone 0.20; ethyl acetate 0.035; diethyl ether <0.001; hexane <0.001; toluene 0.001; N,N-dimethylformamide 10.3; tetrahydrofuran 0.32; 4-methyl-2-pentanone 0.020; propylene glycol 5.64; polyethylene glycol 400 1.40; dimethylsulfoxide 20.5; 2-butanone 0.18. pKa 8.66. Practically insol in H2O at physiological pH (0.002%). Stable, can be stored for several years under normal conditions; not hygroscopic; not affected by light. LD50 in mice (mg/kg): 75 s.c.; 28 i.p.; 105 orally; in rats (mg/kg): 185 orally (Niemegeers).Therapeutic Category
Antidiarrheal.
Keywords
Antidiarrheal