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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The development of subsensitivity to chlorpheniramine.

To assess the development of subsensitivity to antihistamines, titrated prick skin test (PSTs) were performed to seven fivefold dilutions of histamine and either morphine or antigen at specific intervals during therapy. Ten subjects received chlorpheniramine, 24 mg per day, and placebo in a double-blind crossover study. Total wheal area was measured at baseline and after 1, 3, 7, 21, and 24 days. The dose of chlorpheniramine (or placebo) was doubled from days 22 to 24 to assess the response to dosage increase. Serum levels of chlorpheniramine were measured at days 3 and 21 in six patients. Maximal skin test suppression was observed on days 3 or 7. On day 21 there was significantly less (p less than 0.01) suppression of all PSTs than on days 3 or 7. Mean serum chlorpheniramine was 48.7 ng/ml on day 3 and 36.1 ng/ml on day 21 (not significant). There was no significant correlation between changes in serum chlorpheniramine levels and changes in PST suppression. Doubling the dose of chlorpheniramine did not achieve the maximal suppression observed at days 3 or 7. We conclude that subsensitivity to antihistamines develops between 7 and 21 days of therapy and cannot be completely overcome by doubling the dose. The decreased effect does not appear to be due to induced metabolism but may be related to increased H1 receptor number.[1]


  1. The development of subsensitivity to chlorpheniramine. Taylor, R.J., Long, W.F., Nelson, H.S. J. Allergy Clin. Immunol. (1985) [Pubmed]
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