Dimenhydrinat

CRYSTALS

WHITE POWDER

Slightly soluble (1-10 mg/ml at 72 °F) (NTP, 1992)

FREELY SOL IN ALCOHOL, CHLOROFORM; SOL IN BENZENE; SOL IN WATER: ABOUT 3 MG/ML; ALMOST INSOL IN ETHER

Breast Feeding; Lactation; Antihistamines; Antiemetics; Gastrointestinal Agents

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

216 to 225 °F (NTP, 1992)

103-104

102-107 °C

Danger

H302 (99%): Harmful if swallowed [Warning Acute toxicity, oral]

P260, P261, P262, P264, P264+P265, P270, P271, P280, P284, P301+P317, P302+P352, P304+P340, P305+P351+P338, P316, P319, P320, P321, P330, P332+P317, P337+P317, P361+P364, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 105 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

SYMPTOMS: Symptoms associated with this compound include: drowsiness, lethargy, fatigue hypnosis and coma. Initial sedation may be followed by central nervous system hyperexcitability. Also, the victim may experience dry mouth, anorexia, nausea, vomiting, abdominal distress, constipation, and/or diarrhea. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, you should dampen the solid spill material with alcohol, then transfer the dampened material to a suitable container. Use absorbent paper dampened with alcohol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with alcohol followed by washing with a strong soap and water solution. Do not reenter the contaminate area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

CHLORPHENIRAMINE COULD THEORETICALLY PREVENT BETA-ADRENERGIC BLOCKING EFFECT OF PROPRANOLOL & ENHANCE ITS QUINIDINE-LIKE EFFECT. .../ANTIHISTAMINES/ ARE SIMILAR TO CHLORPHENIRAMINE IN THEIR ACTIONS. OTHER ANTIHISTAMINES INCL...DIMENHYDRINATE...

PATIENTS RECEIVING ANTIHISTAMINES SHOULD BE WARNED AGAINST THE CONCOMITANT USE OF ALCOHOLIC BEVERAGES OR OTHER DRUGS THAT DEPRESS CNS... /ANTIHISTAMINES/

...POSSESS SIGNIFICANT ANTICHOLINERGIC ACTIVITY & HAVE PRONOUNCED TENDENCY TO INDUCE SEDATION. /ETHANOLAMINES/

SIDE EFFECT WITH HIGHEST INCIDENCE...IS SEDATION. ... OTHER...REFERABLE TO CENTRAL ACTIONS INCL DIZZINESS, TINNITUS, LASSITUDE, INCOORDINATION, FATIGUE, BLURRED VISION, DIPLOPIA, EUPHORIA, NERVOUSNESS, INSOMNIA, & TREMORS. /ANTIHISTAMINES/

...SIDE EFFECTS...DIGESTIVE TRACT...LOSS OF APPETITE, NAUSEA, VOMITING, EPIGASTRIC DISTRESS, & CONSTIPATION OR DIARRHEA. ...DRYNESS OF MOUTH, THROAT & RESP PASSAGES...COUGH; URINARY FREQUENCY & DYSURIA; PALPITATION, HYPOTENSION, HEADACHE; TIGHTNESS OF CHEST; & TINGLING, HEAVINESS & WEAKNESS OF HANDS. /ANTIHISTAMINES/

IN SMALL CHILD, DOMINANT EFFECT IS EXCITATION...INCL HALLUCINATIONS, EXCITEMENT, ATAXIA, INCOORDINATION, ATHETOSIS, & CONVULSIONS. ...OF INTERMITTENT TONIC-CLONIC TYPE... FIXED, DILATED PUPILS WITH FLUSHED FACE & FEVER... TERMINALLY...DEEPENING COMA WITH CARDIORESPIRATORY COLLAPSE & DEATH... /ANTIHISTAMINES/

For more Human Toxicity Excerpts (Complete) data for DIMENHYDRINATE (9 total), please visit the HSDB record page.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Dimenhydrinate

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

DIMENHYDRAMINE...WAS FOUND NOT TO BE TERATOGENIC TO SPRAGUE-DAWLEY RATS WHEN GIVEN THROUGHOUT PREGNANCY BEGINNING 3 DAYS BEFORE CONCEPTION.

...IN GUINEA PIGS PROTECTED FROM HISTAMINE-INDUCED ASPHYXIAL DEATH BY H1-BLOCKING DRUGS. ...MAY SUBSEQUENTLY DIE FROM PERFORATED ULCERATION AS RESULT OF GASTRIC HYPERSECRETION. /ANTIHISTAMINES/

R - Respiratory system

QR - Respiratory system

Dimenhydrinate is indicated for the prevention and treatment of nausea, vomiting, or vertigo of motion sickness. It has a short duration of action of 4-8 hours. Patients should be counselled regarding pronounced drowsiness, avoiding alcohol and other sedatives, and exercising caution when operating a motor vehicle or heavy machinery.

Dimenhydrinate is a theoclate salt that separates into [diphenhydramine] and [8-chlorotheophylline]. While the exact mechanism of action is unknown, diphenhydramine is theorized to reduce disturbances to equilibrium through antimuscarinic effects or histamine H1 antagonism. 8-chlorotheophylline may produce excitation through blocking adenosine receptors, reducing the drowsiness produced by diphenhydramine.

IT IS ESSENTIAL TO NOTE THAT NEITHER H1...BLOCKERS INHIBIT HISTAMINE RELEASE. ...EFFECTS OF HISTAMINE ANTAGONISTS...FACILITATE RELEASE. BENEFICIAL EFFECTS OF HISTAMINE ANTAGONISTS ARE THUS CONFINED TO ANTAGONISM OF RESPONSES TO HISTAMINE THAT IS RELEASED. /ANTIHISTAMINES/

DRUGS USED TO BLOCK HISTAMINE RECEPTORS FALL INTO THAT LARGE GROUP OF PHARMACOLOGICAL ANTAGONISTS THAT APPEAR TO ACT BY OCCUPYING "RECEPTIVE SITES" ON EFFECTOR CELL, TO EXCLUSION OF AGONIST MOLECULES, WITHOUT THEMSELVES INITIATING RESPONSE. TYPICALLY...COMPETITIVE & REVERSIBLE. /ANTIHISTAMINES/

...ANTIHISTAMINES EFFECTIVE IN MOTION SICKNESS ACT BY VIRTUE OF CENTRAL ANTAGONISM OF ACH... ACT BY BLOCKING EXCITATORY LABYRINTHINE IMPULSES @ CHOLINERGIC SYNAPSES IN REGION OF VESTIBULAR NUCLEI. /ANTIHISTAMINES/

...MOTION SICKNESS. ...STIMULATION OF VESTIBULAR APPARATUS...& THAT VESTIBULAR CEREBELLAR MIDBRAIN "INTEGRATIVE VOMITING CENTER" & MEDULLARY CHEMORECEPTIVE TRIGGER ZONE ARE SOMEHOW INVOLVED. /ANTIHISTAMINES/

Dimenhydrinate is a theoclate salt that separates into [diphenhydramine] and [8-chlorotheophylline]. diphenhydramine can either be N-glucuronidated by UGTs to diphenhydramine N-glucuronide or N-demethylated by CYP2D6, CYP1A2, CYP2C9, and CYP2C19 to N-desmethyldiphenhydramine. N-desmethyldiphenhydramine can be N-demethylated again by the same enzymes to N,N-didesmethyldiphenhydramine, which undergoes oxidative deamination to form diphenylmethoxyacetic acid.

EXTENSIVE STUDIES OF METABOLIC FATE OF ANTIHISTAMINES HAVE BEEN LIMITED TO A FEW COMPD. ... MAIN SITE OF METABOLIC TRANSFORMATION IS LIVER. /ANTIHISTAMINES/

DIMENHYDRINATE

Histamine-1 Receptor Antagonist [EPC]; Histamine H1 Receptor Antagonists [MoA]

Drugs used to prevent NAUSEA or VOMITING.

Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.

A 50 mg oral film coated tablet reaches a Cmax of 72.6 ng/mL with a Tmax of 2.7 hours. A 100 mg suppository reaches a Cmax of 112.2 ng/mL with a Tmax of 5.3 hours.

Dimenhydrinate is predominantly eliminated in the urine. 1-3% of the dissociated diphenhydramine is eliminated in the urine unchanged, while 64% of diphenhydramine is eliminated in the urine as metabolites. The elimination of dimenhydrinate has not been fully studied.

The volume of distribution of dimenhydrinate is 3-4 L/kg.

DIMENHYDRINATE (ETHANOLAMINES): DURATION OF ACTION (HR) 4-6. /FROM TABLE/

H1 ANTAGONISTS ARE READILY ABSORBED FROM GI TRACT & PARENTERAL SITES OF ADMIN. FOLLOWING ORAL ADMIN, EFFECTS START WITHIN 15 TO 30 MIN, ARE FULLY DEVELOPED WITHIN 1 HR, & LAST ABOUT 3 TO 6 HR, ALTHOUGH SOME...ACT LONGER. /ANTIHISTAMINES/

MEDICATION

MEDICATION (VET)

Use (kg; approx.) in Germany (2009): >7500

CUSIC, SCIENCE 109, 574 (1949); CUSIC, US PATENTS 2,499,058 & 2,534,813 (1950 TO SEARLE).

BY CAUSING DIMETHYLAMINOETHYL BENZHYDRYL ETHER TO COMBINE WITH 8-CHLOROTHEOPHYLLINE BY REFLUXING ISOPROPYL ALCOHOL SOLN. CRYSTALLINE PPT OF DIMENHYDRINATE WHICH FORMS ON COOLING IS COLLECTED BY FILTRATION, WASHED WITH COLD ETHYL ACETATE & DRIED.

INJECTION: 50 MG/ML; SUPPOSITORIES: 100 MG; SYRUP USP: 15 MG/5 ML; TABLETS USP: 50 MG.

...CONTAINS 53-55.5% OF DIPHENYLHYDRAMINE (C17-H21-N-O), & 44.47% OF 8-CHLOROTHEOPHYLLINE (C7-H7-CL-N4-O2).