3309. Diphenhydramine

Nomenclature

CAS number: 58-73-1
2-Diphenylmethoxy-N,N-dimethylethanamine; 2-(benzhydryloxy)-N,N-dimethylethylamine; β-dimethylaminoethyl benzhydryl ether; O-benzhydryldimethylaminoethanol; β-dimethylaminoethanol diphenylmethyl ether; α-(2-dimethylaminoethoxy)diphenylmethane; benzhydramine.
C17H21NO; mol wt 255.35.
C 79.96%, H 8.29%, N 5.49%, O 6.27%.

Description and references

Antihistamine with sedating and antiemetic effects. Prepn: G. Rieveschl, Jr., US 2421714 (1947 to Parke, Davis); see also H. Martin et al., US 2397799 (1946 to Geigy). Toxicology study: O. M. Gruhzit, R. A. Fisken, J. Pharmacol. Exp. Ther. 89, 227 (1947). Comprehensive description of the hydrochloride: I. J. Holcomb, S. A. Fusari, Anal. Profiles Drug Subs. 3, 173-232 (1974). Clinical pharmacokinetics: J. M. Scavone et al., J. Clin. Pharmacol. 38, 603 (1998) PubMed. Clinical trial in insomnia: K. Rickels et al., ibid. 23, 235 (1983). Spectrofluorometric determn in pharmaceutical preparations: I. Pascual Reguera et al., Anal. Sci. 20, 799 (2004) DOI PubMed. CE-MS determn in urine: A. Baldacci et al., Electrophoresis 25, 1607 (2004) DOI PubMed.

Chemical structure

Properties

bp2.0 150-165°.

Derivative

Hydrochloride.

Nomenclature

CAS number: 147-24-0
Benadryl (Pfizer); Benocten (Medinova); Nytol (GSK); Sedopretten (Schoening); Sominex (GSK); Unisom Sleepgels (Chattem).
C17H21NO.HCl; mol wt 291.82.
C 69.97%, H 7.60%, N 4.80%, O 5.48%, Cl 12.15%.

Properties

Crystals from abs alcohol + ether, mp 166-170°. Bitter taste. Slowly darkens on exposure to light. Stable under ordinary conditions. One gram dissolves in 1 ml water, 2 ml alcohol, 2 ml chloroform, 50 ml acetone. Very slightly sol in benzene, ether. pH of 1% aq soln about 5.5. The aq soln forms a pink precipitate with satd Reinecke's salt soln. LD50 orally in rats: 500 mg/kg (Gruhzit, Fisken).

Derivative

Di(acefyllinate).

Nomenclature

CAS number: 6888-11-5
1,2,3,6-Tetrahydro-1,3-dimethyl-2,6-dioxo-7H-purine-7-acetic acid compd with 2-(diphenylmethoxy)-N,N-dimethylethanamine (2:1); diphenhydramine bis(theophyllin-7-ylacetate); bietanautine; Nautamine (Sanofi-Aventis).
C35H41N9O9; mol wt 731.75.
C 57.45%, H 5.65%, N 17.23%, O 19.68%.

Description and references

Prepn: M. Mizier, US 2942000 (1960 to Delagrange).

Properties

Crystals, mp 168-170°. Sol in alc; sparingly sol in water.

Therapeutic Category

Antihistaminic; sedative, hypnotic; antiemetic.

Therapeutic Category (Veterinary)

Antihistaminic; antiemetic.

Keywords

Antihistaminic; Aminoalkylethers; Sedative/Hypnotic; Antiemetic