Chemical Properties
white crystalline powder
Uses
A histamine H1-receptor antagonist.
Uses
antihistamine, sedative, treatment of allergic
Uses
Diphenhydramine is a H1-histamine receptor antagonist. Diphenhydramine is categorized as an antihistaminic; sedative, hypnotic.
Uses
H1-Histamine receptor antagonist. Antihistaminic; sedative, hypnotic
Definition
ChEBI: The hydrochloride salt of diphenhydramine.
General Description
White or almost-white crystalline powder. Odorless with a bitter numbing taste. pH (5% aqueous solution) 4-6.
Reactivity Profile
DIPHENHYDRAMINE HYDROCHLORIDE(147-24-0) gives acidic solutions in water. Neutralizes bases. May react with strong oxidizing and strong reducing agents. May catalyze organic reactions. Slowly darkens on exposure to light.
Air & Water Reactions
Water soluble. Aqueous solutions are acidic.
Biological Activity
H 1 receptor antagonist. Antihistamine.
Fire Hazard
Flash point data for this chemical are not available; however, DIPHENHYDRAMINE HYDROCHLORIDE is probably combustible.
Originator
Benadryl,Parke Davis,US,1946
Application
Diphenhydramine hydrochloride is used as an antihistamine and for its antieholinergie (drying) and sedative effects; for allergic conjunctivitis due to foods; for mild, uncomplicated allergic skin manifestations of urticaria and angioedema; for amelioration of allergic reactions to blood or plasma; for dermatographism; in therapy for anaphylaetie reactions adjunctive to epinephrine and other standard measures after the acute manifestations have been controlled; for active and prophylactie treatment of motion sickness; for parkinsonism; an antiemetic; has local anesthetic properties; in preparations for the relief of cough; in the prevention and treatment of radiation sickness, nausea and vomiting; for treatment of allergie cheilitis and stomatitis.
Preparation
Diphenhydramine Hydrochloride synthesis is a four-step sequence starting with a Grignard reaction.
Synthesis of Diphenhydramine Hydrochloride 6.
A) modified synthetic route to diphenhydramine hydrochloride.
B) Sequence of unit operations required for the synthesis. The dotted boxes denote the four stages of the synthesis. DMAE: dimethylaminoethanol.
Organic synthesis in a modular robotic system driven by a chemical programming language
Manufacturing Process
As described in US Patent 2,421,714: (a) benzhydryl
omide is first prepared
as follows: 840 parts by weight of diphenylmethane is heated to 130°C with
stirring. In the presence of a 200 watt electric light 6 inches from the flask,
880 parts of
omine is added slowly. Liberation of H
occurs and addition
requires 1 hour and 45 minutes. The temperature is maintained at 130°C for
an additional 30 minutes. A fine stream of air is blown in to remove H
and
2 while the reaction mixture cools. Benzene (180 parts) is added and the
solution used immediately in (b) below.
If pure benzhydryl
omide is desired the above reaction mixture is dissolved
in ether, washed with water, sodium carbonate solution and finally with water.
The ether is removed, benzene added and distilled off and the benzhydryl
omide distilled in vacuo. Yield 85%.
(b) 490 parts β-dimethylaminoethanol and 530 parts of anhydrous sodium
carbonate are heated to 110°C with stirring. The addition of the benzenebenzhydryl
omide mixture is then begun. The temperature is raised to 120°-
125°C. As reaction takes place carbon dioxide is evolved, the addition requires1? hours. The mixture is kept at 125°C for 5 hours additional time. After
cooling, 3,000 parts of water is added and the mixture stirred until the
inorganic salts are dissolved. The mixture is transferred to a large separatory
funnel and 1,500 parts of ether added. The ether solution is washed several
times with water and then the ether layer extracted with 1 to 4 hydrochloric
acid. The acid solution is treated with 30 parts of Darco and 30 parts Filter-Cel
and filtered.
The free base is liberated from the acid solution with 20% sodium hydroxide
solution and taken up in ether. The ether layer is washed with water, saturated
with NaCl and then shaken with solid potassium hydroxide. The ether is
removed by distillation, 200 parts of benzene added and distilled off. The
residue is distilled in vacuo and the fraction 150°-165°C/2 mm is collected
and amounts to 433 parts. The hydrochloride salt is prepared by dissolving
the free base in anhydrous ether and slowly adding an alcoholic solution of
hydrogen chloride. The solid is recrystallized from absolute alcohol-ether
mixture or isopropanol-ether mixture and has a MP of 161-162°C.
Brand name
Benadryl (Parke-Davis).
Therapeutic Function
Antihistaminic
Health Hazard
Potentially. If taken in large quantities, diphenhydramine can cause severe agitation and confusion, fever, skin flushing, problems with vision, dry mouth, dry eyes, and inability to sweat. Overdoses can lead to high heart rates, abnormal heart rhythms, seizures, and death.
If given to elderly patients, diphenhydramine can cause confusion and agitation. Because of this, diphenhydramine is not recommended in elderly patients for insomnia or treatment for the common cold; though it should still be given in cases of allergic reaction.
Biochem/physiol Actions
H1 histamine receptor antagonistDiphenhydramine hydrochloride (DPH) is an antihistaminic agent that relieves symptoms of hypersensitive reactions. It exhibits antimuscarinic and marked sedative effects. DPH is also used to prevent nausea, vomiting and vertigo of various causes. In addition, it acts as a potential therapeutic for insomnia.
Veterinary Drugs and Treatments
In veterinary medicine, diphenhydramine is used principally for its
antihistaminic
effects, but also for other pharmacologic actions. Its
sedative effects can be of benefit
in treating the agitation (pruritus,
etc.) associated with allergic responses. It has also been used for
treatment and prevention of motion sickness and as an antiemetic
in small animals. It has been suggested for use as adjunctive treatment
of aseptic laminitis in cattle and it may be useful as an adjunctive
treatment for feline pancreatitis. For other suggested uses, refer
to the Dosage section below.
