(+-)-Chlorpheniramine

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. /Chlorpheniramine maleate/ [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=113-92-8]

SYMPTOMATOLOGY: 1. CENTRAL NERVOUS DEPRESSION IS USUALLY DOMINANT REACTION IN ADULTS; IT IS EVIDENCED BY DROWSINESS, LETHARGY, FATIGUE, HYPNOSIS, & COMA. RELATED NERVOUS SYMPTOMS INCL VERTIGO, ATAXIA, TINNITUS, & BLURRED VISION. /ANTIHISTAMINICS/

SYMPTOMATOLOGY: 2. CENTRAL NERVOUS HYPEREXCITABILITY OFTEN FOLLOWS INITIAL SEDATION; IN CHILDREN EXCITEMENT IS OFTEN FIRST EVIDENCE OF POISONING. STIMULANT PHASE BRINGS TREMORS, ANXIETY, INSOMNIA, EXCITEMENT, HALLUCINATIONS, DELIRIUM, TOXIC PSYCHOSIS & CONVULSIONS... /ANTIHISTAMINICS/

SYMPTOMATOLOGY: 3. DANGEROUS HYPERPYREXIA MAY OCCUR IN POISONED CHILDREN... 4. GASTROINTESTINAL REACTIONS INCL DRY MOUTH, ANOREXIA, NAUSEA, VOMITING, ABDOMINAL DISTRESS, CONSTIPATION, &/OR DIARRHEA. /ANTIHISTAMINICS/

SYMPTOMATOLOGY: 5. TERMINAL PHASE IS ONE OF SEVERE CENTRAL NERVOUS DEPRESSION, WITH DEATH FROM RESP ARREST OR CARDIOVASCULAR COLLAPSE. /ANTIHISTAMINICS/

For more Human Toxicity Excerpts (Complete) data for CHLORPHENIRAMINE (10 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

chlorpheniramine

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

LARGE DOSES PRODUCE CONVULSIONS IN EXPTL ANIMALS. /ANTIHISTAMINES/

SMALL DOSES OF SOME ANTIHISTAMINICS PRODUCE DEPRESSION, DROWSINESS, SALIVATION & VOMITING. /ANTIHISTAMINICS/

CHLORPHENIRAMINE MALEATE DECR ACETYLCHOLINE LEVEL IN BOTH HEMISPHERES & REST OF BRAIN. RESULTS FOR STYRAMINE ARE ALSO GIVEN.

... H1 antagonists are eliminated more rapidly by children than by adults and more slowly in those with severe liver disease. /Histamine Antagonists: H1 Antagonists/

CHLORPHENIRAMINE MALEATE, AN ANTAGONIST OF HISTAMINE, INHIBITED DEVELOPMENT OF EHRLICH ASCITES CARCINOMA WHEN GIVEN TO MICE ORALLY FOR 10 DAYS, STARTING ON DAY OF TUMOR IMPLANT.

Use is not recommended in newborn or premature infants because this age group has an increased susceptibility to anticholinergic side effects, such as central nervous system excitation, and an increased tendency toward convulsions. A paradoxical reaction characterized by hyperexcitability may occur in children taking antihistamines. /Antihistamines/

Dizziness, sedation, confusion, and hypotension may be more likely to occur in geriatric patients taking antihistamines. Geriatric patients are especially susceptible to the anticholinergic side effects, such as dryness of mouth and urinary retention (especially in males), of the antihistamines. If these side effects occur and continue or are severe, medication should probably be discontinued. /Antihistamines/

There is no specific therapy for antihistamine poisoning, and treatment is along general symptomatic and supportive lines. ... Should breathing fail, mech support of ventilation offer safer and ... effective means of maintaining resp than use of analeptics which are prone to initiative or intensify convulsive phase. /Antihistamine/

Toxicology and carcinogenesis studies of chlorpheniramine maleate (99% pure) ... were conducted by administering this chemical in deionized water by gavage to 50 male and 50 female F344/N rats and B6C3F1 mice, 5 days/wk for 103 wk. The doses used were: male rats: 0, 15, or 30 mg/kg; female rats: 0, 30, or 60 mg/kg; male mice: 0, 25, or 50 mg/kg; female mice: 0, 100, or 200 mg/kg. ... Under the conditions of these two yr studies, there was no evidence of carcinogenicity for F344/N rats or B6C3F1 mice administered chlorpheniramine maleate in deionized water, 5 days/wk for two yr. Due to high mortality in high dose female rats and high dose male mice, the sensitivity of these groups to detect carcinogenic response was reduced. /The cmpd/ had a proliferative effect on the thyroid gland of female mice, as shown by the increased evidences of follicular cell cysts and hyperplasia in both low dose and high dose groups. /Chlorpheniramine maleate/

21-27 hours

IN MAN...PLASMA T/2 OF CHLORPHENIRAMINE IS...12-15 HR...ALTHOUGH PLASMA LEVELS OF TOTAL RADIOACTIVITY ARE PROLONGED...

Elimination: 14 to 25 hours

Primarily hepatic via Cytochrome P450 (CYP450) enzymes.

MAIN SITE OF METABOLIC TRANSFORMATION IS LIVER. /ANTIHISTAMINES/

Primarily hepatic via Cytochrome P450 (CYP450) enzymes. Half Life: 21-27 hours

3U6IO1965U

CHLORPHENIRAMINE

Mechanisms of Action [MoA] - Histamine H1 Receptor Antagonists

Established Pharmacologic Class [EPC] - Histamine-1 Receptor Antagonist

Chlorpheniramine is a Histamine-1 Receptor Antagonist. The mechanism of action of chlorpheniramine is as a Histamine H1 Receptor Antagonist.

Agents, usually topical, that relieve itching (pruritus).

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.

Agents that are used to treat allergic reactions. Most of these drugs act by preventing the release of inflammatory mediators or inhibiting the actions of released mediators on their target cells. (From AMA Drug Evaluations Annual, 1994, p475)

Well absorbed in the gastrointestinal tract.

STUDIES IN MAN & EXPTL ANIMALS INDICATE THAT (3)H-CHLORPHENIRAMINE MALEATE IS RAPIDLY & QUANT ABSORBED FROM GUT. ALTHOUGH PLASMA LEVELS OF TOTAL RADIOACTIVITY ARE PROLONGED, PLASMA T/2 OF CHLORPHENIRAMINE IS ONLY 12-15 HR IN MAN & 3 HR IN DOG. T/2 IN MAN IS ABOUT 3 TIMES LONGER THAN THERAPEUTIC EFFECT...

The H1 antagonists are well absorbed from the GI tract. Following oral administration, peak plasma concn are achieved in 2 to 3 hr and effects usually last 4 to 6 hr; however, some of the drugs are much longer acting ... . /Histamine Antagonists: H1 Antagonists/

H1 blockers are among the many drugs that induce hepatic microsomal enzymes, and they may facilitate their own metabolism. /Histamine Antagonists: H1 Antagonists/