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- Title
A PET study with [11C]AZ10419369 to determine brain 5-HT1B receptor occupancy of zolmitriptan in healthy male volunteers.
- Authors
Varnäs, Katarina; Jučaitė, Aurelija; McCarthy, Dennis J; Stenkrona, Per; Nord, Magdalena; Halldin, Christer; Farde, Lars; Kanes, Stephen
- Abstract
Aim: To investigate the occupancy at brain 5-hydroxytryptamine (5-HT) 1B receptors in human subjects after administrationof the antimigraine drug zolmitriptan.Methods: Positron emission tomography (PET) studies were undertaken using the radioligand [11C]AZ10419369 in eightcontrol subjects at baseline and after administration of zolmitriptan orodispersible tablets. The subjects were examinedafter two consecutive administrations of 10 mg zolmitriptan, approximately 1 week apart. Two of the subjects weresubsequently examined after administration of 5 mg zolmitriptan. One week after the last administration of zolmitriptanfive of the subjects underwent additional PET measurements without drug pretreatment.Results: After administration of 10 mg zolmitriptan, mean receptor occupancy was 4-5%. No consistent changes in5-HT1B receptor binding were observed for subjects who received 5mg zolmitriptan. There was a statistically significantnegative relationship between binding potential (BPND) and plasma concentration of zolmitriptan and the active metabolite183C91, respectively. All of the five subjects who were examined 1 week after dosing with zolmitriptan showedhigher BPND post drug administration compared with baseline.Conclusion: This is the first demonstration of CNS 5-HT1B receptor occupancy of a triptan. The findings are consistentwith the low receptor occupancy previously reported in PET studies with agonists at other G protein coupled receptors.
- Subjects
BRAIN imaging; SEROTONIN; HEADACHE treatment; MIGRAINE; MEDICAL imaging systems; G proteins; THERAPEUTICS
- Publication
Cephalalgia, 2013, Vol 33, Issue 10, p853
- ISSN
0333-1024
- Publication type
Article
- DOI
10.1177/0333102413476372