Nimodipine potentiates the light-induced suppression of melatonin.
In mammals the phase shifting response of the circadian clock to light can be enhanced by administration of the calcium channel antagonist nimodipine. In the present study we assessed the potential for nimodipine to affect the responsiveness of the human circadian clock to light by measuring the light-induced suppression of melatonin levels in plasma. Seven healthy young subjects (3M, 4F, 27.3 +/- 1.8 years old) were admitted on four occasions to the Clinical Research Center at Northwestern University Medical School. Blood was collected during the night to assess the effect of nimodipine (30 mg, orally, 01:30 h) on plasma melatonin levels in the presence or absence of light (500 lux, 2-3 am). Melatonin levels in plasma were measured by radioimmunoassay. Exposure to light for 1 h suppressed melatonin levels in plasma by nearly 38% relative to samples obtained at the same time in the absence of light (P = 0.013). Nimodipine administration did not modify plasma melatonin levels. However, combined treatment with nimodipine and light suppressed melatonin levels in plasma by 59%. Levels of plasma melatonin were significantly lower following treatment with nimodipine and light than following treatment with placebo/light (P = 0.014). Thus, the calcium channel antagonist nimodipine potentiated the suppressive effect of light on melatonin levels in plasma. These results suggest that the calcium channel antagonist nimodipine may also potentiate the response of the human circadian clock to light, and might thus be useful in combination with phototherapy for the treatment of sleep and circadian rhythm disorders.
Benloucif
S
S
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, IL 60611, USA. s-benloucif@nwu.edu
Bauer
G L
GL
Dubocovich
M L
ML
Finkel
S I
SI
Zee
P C
PC
D000328:Adult; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects*; D005260:Female; D006801:Humans; D008027:Light; D008297:Male; D008550:Melatonin / Q000097:blood*; D009553:Nimodipine / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D009553:Nimodipine; D008550:Melatonin