Chloropyramine

Chloropyramine
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy; category	C[where?];
Routes of; administration	By mouth, intramuscular, topical
Drug class	First-generation antihistamine
ATC code	D04AA09 (WHO) R06AC03 (WHO);
Legal status
Legal status	By mouth: OTC, Injection: Rx-only (RU);
Pharmacokinetic data
Bioavailability	~100%
Metabolism	Extensive hepatic
Onset of action	15–30 min (oral)
Elimination half-life	~14 hours
Excretion	Kidney
Identifiers
	IUPAC name N'-[(4-chlorophenyl)methyl]-N,N-dimethyl-N'-pyridin-2-ylethane-1,2-diamine;
CAS Number	59-32-5 ;
PubChem CID	25295;
DrugBank	DB08800 ;
ChemSpider	23628 ;
UNII	2K3L8O9SOV;
KEGG	D07195 ;
ChEMBL	ChEMBL1194287 ;
CompTox Dashboard (EPA)	DTXSID50207729 ;
ECHA InfoCard	100.000.383
Chemical and physical data
Formula	C16H20ClN3
Molar mass	289.81 g·mol−1
3D model (JSmol)	Interactive image;
	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 first-generation antihistamine drug approved in several Eastern European countries such as Russia for the treatment of allergic conjunctivitis, allergic rhinitis, bronchial asthma, and other atopic (allergic) conditions. Related indications for clinical use include angioedema, allergic reactions to insect bites, food and drug allergies, and anaphylactic shock.^{[citation needed]}

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 such as drowsiness, weakness, vertigo, fatigue, dry mouth, constipation, and rarely — visual disturbances and increase of intraocular pressure.^{[citation needed]}

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] It should be used with caution in patients with hyperthyroidism, cardiovascular diseases, and asthma.^{[citation needed]}

Adverse effects

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.^{[citation needed]}

A large study on people 65 years old or older linked the development of Alzheimer's disease and other forms of dementia to the "higher cumulative" use of first-generation antihistamines, due to their anticholinergic properties.^[3]

Interactions

Chloropyramine should not be used internally with MAO inhibitors. Because of its anticholinergic activity, concurrent administration with cholinomimetics is not advisable. Chloropyramine should also not be used internally with alcohol, sedatives, and hypnotics because of the potentiation of the effects. General anesthetics, opioids, and other depressants potentiate the sedative effect of chloropyramine.^{[citation needed]}

Dosage

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.^{[citation needed]}

Trade names

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

Synthesis

The preparation begins with the condensation of 4-chlorobenzaldehyde with 1,1-dimethyethylenediamine. The resulting Schiff base is reduced. The resulting amine is then further reacts with 2-bromopyridine in the presence of sodamide.

References

^ ^a ^b ^c "Chloropyramine Tablets for Oral Use. Prescribing Information". State Register of Medicines (in Russian). Ozon OOO. Retrieved 5 January 2016.
^ ^a ^b ^c "Хлоропирамин (Chloropyraminum)" (in Russian).
^ Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, et al. (March 2015). "Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study". JAMA Internal Medicine. 175 (3): 401–407. doi:10.1001/jamainternmed.2014.7663. PMC 4358759. PMID 25621434.
^ Vaughan JR, Anderson GW (March 1949). "Antihistamine agents; halogenated N,N-dimethyl-N-benzyl-N-(2-pyridyl)-ethylenediamines". The Journal of Organic Chemistry. 14 (2): 228–34. doi:10.1021/jo01154a006. PMID 18117722.
^ US granted 2569314, Kenneth HL, "N, n-dimethyl-n'-(4-halobenzyl)-n'-(2-pyridyl) ethylenediamines and preparation of the same", issued 1951, assigned to American Cyanamide
^ US granted 2607778, Cates EM, Phillips RF, "Process of preparing n, n-dimethyln'-(p-chlorobenzyl)-n'-(2-pyridyl)-ethylenediamine", issued 1952, assigned to Merck & Co.
^ CH granted 264754, "Verfahren zur Herstellung eines Äthylendiaminderivates.", issued 1950, assigned to J. R. Geigy AG
^ CH granted 266234, "Verfahren zur Herstellung eines Äthylendiaminderivates.", issued 1950, assigned to J. R. Geigy AG
^ CH granted 266235, "Verfahren zur Herstellung eines Äthylendiaminderivates.", issued 1950, assigned to J. R. Geigy AG
^ GB granted 651596, "Manufacture of n-(2-pyridyl)-n-(p-chloro-benzyl)-n:n-dimethyl-ethylenediamine", issued 1951, assigned to J. R. Geigy AG

[PI-1] "Chloropyramine Tablets for Oral Use. Prescribing Information". State Register of Medicines (in Russian). Ozon OOO. Retrieved 5 January 2016.

[lsgeotar-2] "Хлоропирамин (Chloropyraminum)" (in Russian).

[3] Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, et al. (March 2015). "Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study". JAMA Internal Medicine. 175 (3): 401–407. doi:10.1001/jamainternmed.2014.7663. PMC 4358759. PMID 25621434.

[4] Vaughan JR, Anderson GW (March 1949). "Antihistamine agents; halogenated N,N-dimethyl-N-benzyl-N-(2-pyridyl)-ethylenediamines". The Journal of Organic Chemistry. 14 (2): 228–34. doi:10.1021/jo01154a006. PMID 18117722.

[5] US granted 2569314, Kenneth HL, "N, n-dimethyl-n'-(4-halobenzyl)-n'-(2-pyridyl) ethylenediamines and preparation of the same", issued 1951, assigned to American Cyanamide

[6] US granted 2607778, Cates EM, Phillips RF, "Process of preparing n, n-dimethyln'-(p-chlorobenzyl)-n'-(2-pyridyl)-ethylenediamine", issued 1952, assigned to Merck & Co.

[7] CH granted 264754, "Verfahren zur Herstellung eines Äthylendiaminderivates.", issued 1950, assigned to J. R. Geigy AG

[8] CH granted 266234, "Verfahren zur Herstellung eines Äthylendiaminderivates.", issued 1950, assigned to J. R. Geigy AG

[9] CH granted 266235, "Verfahren zur Herstellung eines Äthylendiaminderivates.", issued 1950, assigned to J. R. Geigy AG

[10] GB granted 651596, "Manufacture of n-(2-pyridyl)-n-(p-chloro-benzyl)-n:n-dimethyl-ethylenediamine", issued 1951, assigned to J. R. Geigy AG

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v t e Antipruritics (D04)
Antihistamines for topical use	Bamipine Chloropyramine Chlorphenoxamine Clemastine Dimetindene Diphenhydramine Isothipendyl Mepyramine Pheniramine Promethazine Thenalidine Thonzylamine Tolpropamine Tripelennamine
Anesthetics for topical use	Benzocaine Cinchocaine Dibucaine Lidocaine Oxybuprocaine Pramocaine Quinisocaine Tetracaine
Others	Corticosteroids (e.g., hydrocortisone) Counterirritants (e.g., mint oil, menthol, camphor) Difelikefalin Doxepin Nalfurafine

v t e Antihistamines (R06)
Benzimidazoles (*)	Astemizole Azelastine Bilastine Emedastine Mizolastine Talastine
Diarylmethanes	Diarylmethoxyalkylamines: Bromazine (bromodiphenhydramine) Carbinoxamine Chlorphenoxamine Clemastine Diphenhydramine (+naproxen) Diphenylpyraline Doxylamine Ebastine Orphenadrine Diphenylmethanolpiperidines: Fexofenadine Terfenadine Diphenylmethylpiperazines: Buclizine Cetirizine Levocetirizine Chlorcyclizine Cinnarizine Cyclizine Etodroxizine Hydroxyzine Meclizine Oxatomide Phenylpyridinylpropanamines: Brompheniramine Chlorphenamine Dexbrompheniramine (+pseudoephedrine) Dexchlorpheniramine (+betamethasone) Pheniramine Others: Acrivastine Bamipine Dimetindene Phenyltoloxamine Pyrrobutamine Quifenadine Triprolidine
Ethylenediamines	Antazoline Chloropyramine Histapyrrodine Mepyramine (pyrilamine) Methapyrilene Phenbenzamine Thenalidine Tripelennamine (pyribenzamine)
Tricyclics	Dibenzocycloheptenes: Antidepressants (e.g., amitriptyline) Azatadine Cyproheptadine Deptropine Desloratadine Ketotifen Loratadine Rupatadine Phenothiazines: Alimemazine Fenethazine Hydroxyethylpromethazine Isothipendyl Mequitazine Methdilazine Oxomemazine Promethazine Others: Antidepressants (e.g., doxepin, mirtazapine, trimipramine) Epinastine Latrepirdine Mebhydrolin Olopatadine Perlapine Phenindamine Pimethixene
Others	Phenylpiperazines: Antidepressants (e.g., trazodone) Phenbenzamine
For topical use	Bamipine Chloropyramine Chlorphenoxamine Clemastine Dimetindene Diphenhydramine Doxepin Isothipendyl Mepyramine (pyrilamine) Promethazine

Clinical data

AHFS/Drugs.com	International Drug Names
Pregnancy category	C^[where?]
Routes of administration	By mouth, intramuscular, topical
Drug class	First-generation antihistamine
ATC code	D04AA09 (WHO) R06AC03 (WHO)
Legal status
Legal status	By mouth: OTC, Injection: Rx-only (RU)
Pharmacokinetic data
Bioavailability	~100%^[1]
Metabolism	Extensive hepatic
Onset of action	15–30 min (oral)^[2]
Elimination half-life	~14 hours^[2]
Excretion	Kidney^[2]
Identifiers
IUPAC name N'-[(4-chlorophenyl)methyl]-N,N-dimethyl-N'-pyridin-2-ylethane-1,2-diamine
CAS Number	59-32-5^Y
PubChem CID	25295
DrugBank	DB08800^Y
ChemSpider	23628^Y
UNII	2K3L8O9SOV
KEGG	D07195^Y
ChEMBL	ChEMBL1194287^N
CompTox Dashboard (EPA)	DTXSID50207729
ECHA InfoCard	100.000.383
Chemical and physical data
Formula	C₁₆H₂₀ClN₃
Molar mass	289.81 g·mol⁻¹
3D model (JSmol)	Interactive image
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^Y Key:ICKFFNBDFNZJSX-UHFFFAOYSA-N^Y
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