Chloropyramine

Chloropyramine

Systematic (IUPAC) name
N'-[(4-chlorophenyl)methyl]-N,N-dimethyl-N'-pyridin-2-ylethane-1,2-diamine
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy category	C
Routes of administration	Oral (tablets), IM, IV, topical
Legal status	Tablets — OTC, solution for injection — ℞-only (RU)
Pharmacokinetic data
Bioavailability	~100%[1]
Metabolism	Extensive hepatic
Onset of action	15–30 min (oral)
Identifiers
CAS Number	59-32-5
ATC code	D04AA09 (WHO) R06AC03
PubChem	CID 25295
DrugBank	DB08800
ChemSpider	23628
UNII	2K3L8O9SOV
KEGG	D07195
ChEMBL	CHEMBL1194287
Chemical data
Formula	C16H20ClN3
Molar mass	289.803 g/mol
SMILES Clc1ccc(cc1)CN(c2ncccc2)CCN(C)C
InChI InChI=1S/C16H20ClN3/c1-19(2)11-12-20(16-5-3-4-10-18-16)13-14-6-8-15(17)9-7-14/h3-10H,11-13H2,1-2H3 Key:ICKFFNBDFNZJSX-UHFFFAOYSA-N
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Chloropyramine is a classical ("old" or first generation) antihistamine drug approved in some Eastern European countries (like Russia) for the treatment of allergic conjunctivitis, allergic rhinitis, bronchial asthma, and other atopic (allergic) conditions. Related indications for clinical use include angioedema (Quincke's edema), allergic reactions to insect bites, food and drug allergies, and anaphylactic shock.

Chloropyramine is known as a competitive reversible H₁ receptor antagonist (also known as an H₁ inverse agonist), meaning that it exerts its pharmacological action by competing with histamine for the H₁ subtype histamine receptor. By blocking the effects of histamine, the drug inhibits the vasodilation, increased vascular permeability, and tissue edema associated with histamine release in the tissue. The H₁ antagonistic properties of chloropyramine can be used by researchers for the purposes of blocking the effects of histamine on cells and tissues. In addition, chloropyramine has some anticholinergic properties.^[1]

Chloropyramine's anticholinergic properties and the fact that it can pass through the blood–brain barrier are linked to its clinical side effects: drowsiness, weakness, vertigo, fatigue, dryness in the mouth, constipation, and rarely — visual disturbances and increase of intraocular pressure.

Clinical dosage and administration

In cases of severe allergic reactions, chloropyramine can be injected intramuscularly or intravenously. Oral administration: In adults, 25 mg can be taken 3 to 4 times daily (up to 150 mg); in children over 5 years old, 25 mg can be taken 2 to 3 times daily. For external application, the skin or the eye conjunctiva can be treated up to several times a day by applying a thin layer of cream or ointment containing 1% chloropyramine hydrochloride.

Contraindications

Contraindications for parenteral or oral administration include benign prostatic hyperplasia, peptic ulcer, pyloric and duodenal stenosis, uncontrolled glaucoma, pregnancy and breast-feeding. It is not intended for the management of acute bronchospasm.^[1]

Special warnings and precautions

Chloropyramine should not be used internally with alcohol, sedative drugs and hypnotics because of the potentiation of the effects. It should be used with caution in patients suffering from hyperthyroidism, cardiovascular diseases and asthma. In children, it can induce agitation, and in many adult patients dizziness may be observed. Because of the pronounced sedative effect the preparation should be prescribed cautiously in drivers and people working with machines.

Drug interactions

Chloropyramine should not be used internally with MAO inhibitors. Because of its anticholinergic activity, concurrent administration with cholinomimetics is not advisable. General anesthetics, analgesic agents and psycholeptics potentiate the sedative effect of chloropyramine.

Trade names

• Allergosan, Sopharma AD (BG, GE, LV)
• Suprastin, Egis Pharmaceuticals PLC (GE, HU, LT, LV, RU)
• Supralgon, Biopharm JSC (GE)
• Supranorm-Tsiteli A, Rompharm Co. (GE)
• Synopen, Pliva d.o.o. (BA, HR, RS)

Synthesis

Chloropyramine synthesis:^{[2][3][4][5][6][7][8]}

4-chlorobenzaldehyde is condensed with 1,1-dimethylethylenediamine; schiff base is reduced, residue is then further reacted with 2-bromopyridine in the presence of sodamide.

Chloropyramine synthesis 2: U.S. Patent 2,607,778

Chloropyramine synthesis 3: GB 651596 

See also

• Mepyramine (4-methoxy analog)
• Methapyrilene
• Chlorothen

References

1. "Chloropyramine Tablets for Oral Use. Prescribing Information". State Register of Medicines (in Russian). Ozon OOO. Retrieved 5 January 2016.
2. Vaughan, J. R.; Anderson, G. W.; Clapp, R. C.; Clark, J. H.; English, J. P.; Howard, K. L.; Marson, H. W.; Sutherland, L. H.; Denton, J. J. (1949). "Antihistamine agents; halogenated N,N-dimethyl-N-benzyl-N-(2-pyridyl)-ethylenediamines". Journal of Organic Chemistry 14 (2): 228–234. doi:10.1021/jo01154a006. PMID 18117722.
3. H.L. Kenneth, U.S. Patent 2,569,314 (1951).
4. E.M. Cates, R.F. Phillips, U.S. Patent 2,607,778 (1952).
5. J.R. Geigy AG., CH 264754  (1950).
6. J.R. Geigy AG., CH 266234  (1950).
7. J. R. Geigy AG., CH 266235  (1950).
8. J.R. Geigy AG., GB 651596  (1951).