title: A PET study with [11C]AZ10419369 to determine brain 5-HT1B receptor occupancy of zolmitriptan in healthy male volunteers.
abstract: OBJECTIVE
  To investigate the occupancy at brain 5-hydroxytryptamine (5-HT) 1B receptors in human subjects after administration of the antimigraine drug zolmitriptan.
  
  
  METHODS
  Positron emission tomography (PET) studies were undertaken using the radioligand [(11)C]AZ10419369 in eight control subjects at baseline and after administration of zolmitriptan orodispersible tablets. The subjects were examined after two consecutive administrations of 10 mg zolmitriptan, approximately 1 week apart. Two of the subjects were subsequently examined after administration of 5 mg zolmitriptan. One week after the last administration of zolmitriptan five 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 in 5-HT1B receptor binding were observed for subjects who received 5 mg zolmitriptan. There was a statistically significant negative relationship between binding potential ( BP ND) and plasma concentration of zolmitriptan and the active metabolite 183C91, respectively. All of the five subjects who were examined 1 week after dosing with zolmitriptan showed higher BP ND post drug administration compared with baseline.
  
  
  CONCLUSIONS
  This is the first demonstration of CNS 5-HT1B receptor occupancy of a triptan. The findings are consistent with the low receptor occupancy previously reported in PET studies with agonists at other G protein coupled receptors.
authors: Karolinska Institutet, Department of Clinical Neuroscience, SE-17176 Stockholm, Sweden. katarina.varnas@ki.se
authors: Katarina
authors: K
authors: Varnäs
authors: Aurelija
authors: A
authors: Jučaite
authors: Dennis J
authors: DJ
authors: McCarthy
authors: Per
authors: P
authors: Stenkrona
authors: Magdalena
authors: M
authors: Nord
authors: Christer
authors: C
authors: Halldin
authors: Lars
authors: L
authors: Farde
authors: Stephen
authors: S
authors: Kanes
mesh_terms: D000328:Adult; D001578:Benzopyrans / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000378:metabolism; D006801:Humans; D008297:Male; D009025:Morpholines / Q000378:metabolism*; D023303:Oxazolidinones / Q000378:metabolism*; D010879:Piperazines / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000378:metabolism*; D014363:Tryptamines / Q000378:metabolism*; D055815:Young Adult
chemical_list: C530629:5-methyl-8-(4-methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (4-morpholin-4-yl-phenyl)amide; D001578:Benzopyrans; D002250:Carbon Radioisotopes; D009025:Morpholines; D023303:Oxazolidinones; D010879:Piperazines; D044302:Receptor, Serotonin, 5-HT1B; D058825:Serotonin 5-HT1 Receptor Agonists; D014363:Tryptamines; C089750:zolmitriptan
keywords: 5-HT1B receptors; Brain imaging; PET; serotonin; zolmitriptan