Lack of effect of chloroquine on pupillary size in man

Abstract

Chloroquine causes pruritus similar to that seen with opiates. It has been suggested that chloroquine (C) induced pruritus may be caused by mu opiate receptor activation. We therefore examined the effect of chloroquine on pupillary size as a marker of central mu opiate receptor activation in 12 healthy subjects of African descent with prior exposure to C, 6 with and 6 without history of chloroquine-induced pruritus. In a single blind, sequential dosing design, subjects received a single oral dose of morphine sulphate (M, 10mg), placebo (P) pills and C (600mg base). Pupillary size was evaluated before and 0.5, 1, 2, 4, 8,12 and 24 hours after dosing. Pruritus and DSST were assessed before and 0, 4, 8, 12 and 24 hours after dosing. The patients were aged 30(±4) years and had a BMI of 24(±2) kgm-2. Historical itchers to chloroquine (H+) and historical non-itchers (H-) were well matched for age, BMI, liver and renal function. When the whole group (H+ and H−) was analyzed (n=12), M caused significant pupillary constriction compared to C or P (p<0.001, T test for linear mixed model). There is no significant difference when C is compared to P. Chloroquine caused itching in 66% of historical itchers (4/6) compared to 0% of non-itchers (p<0.05, fishers exact test). We conclude that chloroquine does not cause miosis in man and direct mu opiate activation is not a likely mechanism for chloroquine-induced pruritus. Clinical Pharmacology & Therapeutics (2004) 75, P64–P64; doi: 10.1016/j.clpt.2003.11.242