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.
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 with
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.
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]
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.
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.
^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.
PMID18117722.
^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