H1 Receptor ( Kd = 6.06 nM )

Brompheniramine (0.1-100 μM) blocks hERG K+ channels expressed in CHO cells in a concentration-dependent manner with an IC50 of 0.90±0.14 μM, and lowers the peak tail current amplitude measured at -60 mV (cells are depolarized from a holding potential of -80 mV to +20 mV for 2 s, and then they repolarize for 3 s to return to -60 mV)[3].
Brompheniramine (1, 10 and 100 μM) considerably shortens the APD50, depresses the plateau phase of the action potential, and slightly prolongs the APD90 at 10 and 100 μM in guinea pig papillary muscle[3].
Brompheniramine (0.1-100 μM) inhibits the amplitude of the Ca2+ channel currents in rat ventricular myocytes by 14.1±1.1, 31.1±5.8, 38.0±3.8, and 90.2±3.7% at 0.1, 1, 10 and 100 μM, respectively[3].
Brompheniramine inhibits muscarinic cholinergic receptors in human chinese hamster ovary (CHO) cells[4].

Brompheniramine (0.3-3 μM; SC, single dosage) causes cutaneous analgesia in rats[1].

Some antihistamines (mainly terfenadine and astemizole) have been demonstrated to cause QT interval prolongation and, in some cases, torsade-de-pointes. We investigated the cardiac electrophysiological effects of brompheniramine, a conventional antihistamine. Brompheniramine was reported to prolong QT interval in isolated hearts. To evaluate the electrophysiological effects of brompheniramine, we used whole-cell patch clamp techniques in human ether-a-go-go related gene (hERG)-stably transfected CHO cells, the SCN5A sodium channel transiently transfected CHO cells, and rat myocytes and conventional microelectrode recording techniques in isolated guinea pig papillary muscles. As for the I(hERG), the IC(50) value of brompheniramine was found to be 0.90+/-0.14microM with a Hill coefficient (n(H)) of 1.75+/-0.42. Action potential duration at 90% repolarization (APD(90)) was slightly prolonged by brompheniramine at 10 and 100microM, but APD(50) was shortened by 100microM. Moreover, despite the potent hERG current block, reductions of the V(max) and total amplitude of action potential were observed at high concentrations of brompheniramine. The change in action potential parameters and poor correlations between hERG and APD assay indicated additional effects of brompheniramine on non-hERG channels. In agreement with this hypothesis, the inhibition of I(Na) (IC(50) values: 21.26+/-2.52microM) and I(Ca) (IC(50) values: 16.12+/-9.43microM) by brompheniramine was observed. The results of this study suggest that brompheniramine may possess classes III, Ib and IV properties, especially at high concentrations and that additional studies on non-hERG channels will be necessary to elucidate the complex electrophysiological effects of brompheniramine on the heart[3].

Anticholinergic effects are presumed to be the mechanism for the efficacy of chlorpheniramine in symptomatic relief of the common cold. Terfenadine, a second-generation antihistamine, reportedly lacks anticholinergic side effects. We evaluated affinities of two commonly used over-the-counter antihistamines, brompheniramine and chlorpheniramine, as well as terfenadine in comparison with atropine at the five human muscarinic cholinergic receptor subtypes using CHO cells stably transfected with the individual subtypes. Atropine was more potent than all three drugs at m1-m5 (p<0.01). No significant difference was observed between chlorpheniramine and brompheniramine. Atropine, brompheniramine, and chlorpheniramine could not discriminate between m1-m5. Terfenadine demonstrated subtype selectivity at m3. In vitro comparisons in human muscarinic receptor subtypes could potentially be used to predict clinical anticholinergic effects of antihistamines and to target receptor-specific effects of such agents[4].

Male Sprague-Dawley rats
0.3, 0.6, 1.1, 1.5 and 3.0  μM
SC, single dosage

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Brompheniramine as an antihistamine blocked sodium channels, and local anesthetics by blocking sodium channels produced the local anesthetic effects. The authors aimed to assess local anesthetic quality and duration of brompheniramine when compared to the local anesthetic mepivacaine. After rats were shaved and injected subcutaneously on the dorsal skin, the panniculus reflex, induced via applying a noxious pinprick to the skin (injected area), was scored. The dose-response curve and nociceptive block duration of brompheniramine were constructed and compared with mepivacaine. The cutaneous analgesic effects in both brompheniramine and mepivacaine groups were concentration-dependent. On the basis of the amount required to produce a 50% block effect (ED50, 50% effective dose), the drug's potency was brompheniramine (0.89 [0.82-0.96] μmol) better than mepivacaine (2.45 [2.17-2.76] μmol) (P < 0.01). Full recovery time of brompheniramine was more prolonged than mepivacaine's (P < 0.01) on infiltrative cutaneous analgesia when comparing ED25s, ED50s and ED75s. Our preclinical data demonstrated that subcutaneous brompheniramine induces dose-relatedly analgesic effects, and brompheniramine induces prolonged analgesic duration when compared with mepivacaine. Brompheniramine also provokes better cutaneous analgesia than mepivacaine.[1]

Absorption
Antihistamines are well absorbed from the gastrointestinal tract after oral administration.
Brompheniramine and dexbrompheniramine maleates appear to be well absorbed from the GI tract.

Distribution of brompheniramine into human body tissues and fluids has not been fully characterized, but the drug appears to be widely distributed. Following oral administration of a single dose of the drug in healthy adults, the apparent volume of distribution reportedly averaged 11.7 L/kg.

Following oral administration of a single 0.13-mg/kg dose of brompheniramine maleate in healthy, fasting adults in one study, peak serum brompheniramine concentrations of 7.7-15.7 ng/mL occurred within 2-5 hours; in most of these individuals, a second lower peak, possibly secondary to enterohepatic circulation, also was observed. The antihistamine effect of brompheniramine, as determined by suppression of the wheal and flare responses induced by intradermal administration of histamine, appears to be maximal within 3-9 hours after a single oral dose of the drug, but suppression of the flare response may persist for up to at least 48 hours; the antipruritic effect appears to be maximal within 9-24 hours. American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 10

Brompheniramine and its metabolites are excreted principally in urine. About 40% of an oral dose of brompheniramine is excreted in urine and about 2% in feces within 72 hours in healthy individuals. In healthy individuals, about 5-10% of an oral dose is excreted in urine as unchanged drug ... . American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 10

The pharmacokinetics and antihistaminic effect of brompheniramine in seven normal adults /were assessed/. The mean peak serum brompheniramine concentration of 11.6 +/- 3.0 ng/mL occurred at a mean time of 3.1 +/- 1.1 hr. The mean serum half-life value was 24.9 +/- 9.3 hr, the mean clearance rate was 6.0 +/- 2.3 mL/min/kg, and the mean volume of distribution was 11.7 +/- 3.1 L/kg. The mean wheal size was significantly suppressed (P less than or equal to 0.1) at 3, 6, and 9 hr after the brompheniramine dose when mean concentrations ranged from 10.2 +/- 2.9 to 7.0 +/- 2.2 ng/mL. Significant suppression (P less than or equal to 0.05) of mean flare size was found from 3 to 48 hr after the brompheniramine dose, when mean concentrations ranged from 10.2 +/- 2.9 to 2.5 +/- 0.6 nL/mL. The mean pruritus score was significantly suppressed at 9 and 12 hr (P less than or equal to 0.1) and at 24 hr (P less than or equal to 0.05). Brompheniramine had a long half-life and large volume of distribution in normal adults. It also had a prolonged antihistaminic effect in the skin as evidenced by suppression of the wheal and flare response to histamine and by suppression of pruritus. PMID:6128358 Simons EE et al; J Allergy Clin Immunol 70 (6): 458-64 (1982)

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Metabolism / Metabolites
Hepatic (cytochrome P-450 system), some renal.
The metabolic and excretory fate of the drug has not been fully characterized. Brompheniramine undergoes N-dealkylation to form monodesmethylbrompheniramine and didesmethylbrompheniramine, and is metabolized to the propionic acid derivative, which is partially conjugated with glycine, and to other unidentified metabolites. Brompheniramine and its metabolites are excreted principally in urine. About 40% of an oral dose of brompheniramine is excreted in urine and about 2% in feces within 72 hours in healthy individuals. In healthy individuals, about 5-10% of an oral dose is excreted in urine as unchanged drug, 6-10% as monodesmethylbrompheniramine, 6-10% as didesmethylbrompheniramine, small amounts as the propionic acid derivative and its glycine conjugate, and the remainder as unidentified metabolites.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 10

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Biological Half-Life
the pharmacokinetics and antihistaminic effect of brompheniramine in seven normal adults /were assessed/. ... The mean serum half-life value was 24.9 +/- 9.3 hr ... PMID:6128358 Simons EE et al; J Allergy Clin Immunol 70 (6): 458-64 (1982)

In healthy adults, the half-life of brompheniramine reportedly ranges from 11.8-34.7 hours.

5281067 rat LD50 oral 318 mg/kg
5281067 rat LD50 intraperitoneal 76 mg/kg

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Toxicity Summary
Brompheniramine works by acting as an antagonist of the H1 histamine receptors. It also functions as a moderately effective anticholingeric agent, likely an antimuscarinic agent similar to other common antihistamines such as diphenhydramine. Its effects on the cholinergic system may include side-effects such as drowsiness, sedation, dry mouth, dry throat, blurred vision, and increased heart rate.

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Small, occasional doses of brompheniramine would not be expected to cause any adverse effects in breastfed infants. Larger doses or more prolonged use may cause effects in the infant or decrease the milk supply, particularly in combination with a sympathomimetic such as pseudoephedrine or before lactation is well established. Single bedtime doses after the last feeding of the day may be adequate for many women and will minimize any effects of the drug. The nonsedating antihistamines are preferred alternatives.

◉ Effe
cts in Breastfed Infants Irritability and disturbed sleep were reported in an 11-week-old breastfed infant whose mother was taking a product containing dexbrompheniramine and etafedrine (d-isoephedrine). These side effects were possibly caused by dexbrompheniramine in breastmilk, but could have been caused by the etafedrine or both drugs.
In one telephone follow-up study, mothers reported irritability and colicky symptoms in 10% of infants exposed to various antihistamines and drowsiness was reported in 1.6% of infants. None of the reactions required medical attention and none of the infants were exposed to brompheniramine or dexbrompheniramine.

◉ Effects on Lactation and Breastmilk
Antihistamines in relatively high doses given by injection can decrease basal serum prolactin in nonlactating women and in early postpartum women. However, suckling-induced prolactin secretion is not affected by antihistamine pretreatment of postpartum mothers. Whether lower oral doses of brompheniramine have the same effect on serum prolactin or whether the effects on prolactin have any consequences on breastfeeding success have not been studied. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

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Exposure Routes
Antihistamines are well absorbed from the gastrointestinal tract after oral administration. Toxin and Toxin Target Database (T3DB)

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Symptoms
Signs of overdose include fast or irregular heartbeat, mental or mood changes, tightness in the chest, and unusual tiredness or weakness.

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Toxicity Data
Oral, Rat: LD₅₀ = 318 mg/kg.

[1]. Subcutaneous brompheniramine for cutaneous analgesia in rats. Eur J Pharmacol. 2019 Oct 5;860:172544.

[2]. Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65.

[3]. Electrophysiological effects of brompheniramine on cardiac ion channels and action potential. Pharmacol Res. 2006 Dec;54(6):414-20.

[4]. Affinities of brompheniramine, chlorpheniramine, and terfenadine at the five human muscarinic cholinergic receptor subtypes. Pharmacotherapy. 1999 Apr;19(4):447-51.

Brompheniramine maleate is the maleic acid salt of brompheniramine. A histamine H1 receptor antagonist, it is used for the symptomatic relief of allergic conditions, including rhinitis and conjunctivitis. It has a role as an anti-allergic agent. It contains a brompheniramine.
Brompheniramine Maleate is the maleate salt form of brompheniramine, an alkylamine derivative and a histamine antagonist with anticholinergic and sedative properties. Brompheniramine maleate competes with histamine for the H1 receptor. This diminishes the actions of histamine on effector cells and decreases the histamine-mediated symptoms of allergic reaction such as bronchoconstriction, vasodilation, increased capillary permeability and spasmodic contractions of gastrointestinal smooth muscle.
Histamine H1 antagonist used in treatment of allergies, rhinitis, and urticaria.
See also: ... View More ...

C20H23BRN2O4

435.31

434.084

C, 55.18; H, 5.33; Br, 18.36; N, 6.44; O, 14.70

980-71-2

Brompheniramine; 86-22-6

5281067

White solid powder

403ºC at 760 mmHg

134-135ºC

3.639

2

6

7

27

368

0

BrC1C([H])=C([H])C(=C([H])C=1[H])C([H])(C1=C([H])C([H])=C([H])C([H])=N1)C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])[H].O([H])C(/C(/[H])=C(\[H])/C(=O)O[H])=O

SRGKFVAASLQVBO-BTJKTKAUSA-N

InChI=1S/C16H19BrN2.C4H4O4/c1-19(2)12-10-15(16-5-3-4-11-18-16)13-6-8-14(17)9-7-13;5-3(6)1-2-4(7)8/h3-9,11,15H,10,12H2,1-2H3;1-2H,(H,5,6)(H,7,8)/b;2-1-

3-(4-bromophenyl)-N,N-dimethyl-3-pyridin-2-ylpropan-1-amine;(Z)-but-2-enedioic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (5.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (5.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 25 mg/mL (57.43 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)