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Exquisite delineation of 5-HT1A receptors in human brain with PET and [carbonyl-11C]WAY-100635

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Abstract

The 5-HT1A receptor antagonist, WAY-100635 [N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide], was labelled in its carbonyl group with carbon-11 (t12 = 20.4 min), injected intravenously into healthy male volunteers and studied with positron emission tomography (PET). The acquired data provide exquisite delineation of 5-HT1A receptors in brain, with the ratio of radioactivity uptake in receptor-rich regions, such as medial temporal cortex, to that in receptor-devoid cerebellum reaching 25 by 60 min after radioligand injection. Application of biomathematical modelling to the data revealed high values (7.8) for binding potential, a measure of BmaxKD, in receptor-rich regions. Only very polar radioactive metabolites were present in plasma, a finding consistent with the low level of nonspecific binding seen in cerebellum. [carbonyl-11C]WAY-100635 is concluded to be far superior to the previously reported [O-methyl-11C]WAY-100635 as a radioligand for PET studies of 5-HT1A receptors in human brain.

References (8)

  • V.W. Pike et al.

    First delineation of 5-HT1A receptors in human brain with PET and [11C]WAY-100635

    Eur. J. Pharmacol.

    (1995)
  • I.A. Cliffe

    The design of selective 5-HT1A receptor antagonists

  • A. Fletcher et al.

    A pharmacological profile of WAY 100635, a potent and highly effective 5-HT1A receptor antagonist

    Br. J. Pharmacol.

    (1993)
  • Lammertsma, A.A., C.J. Bench, S.P. Hume, S. Osman, K. Gunn, D.J. Brooks and R.S.J. Frackowiak, 1996, Comparison of...
There are more references available in the full text version of this article.

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    There are a number of possible explanations for this finding: (1) There could be a specific binding component of the [11C]WAY100635 signal in the cerebellum, which is reduced following a blocking dose of GSK588045. This is thought to be unlikely since the cerebellum is believed to have a low level of specific binding of [11C]WAY-100635 (Burnet et al., 1997; Hall et al., 1997), and whilst 5-HT1A is present in the vermis, the cerebellar hemispheres which are composed of largely of white matter have been shown to be devoid of 5-HT1A receptor binding (Parsey et al., 2005; Pazos et al., 1987; Pike et al., 1996); (2) There could be a “spill-over” of signal from brain adjacent areas into the cerebellum. This effect would be more pronounced during the baseline scans, and diminished in the blocked condition, resulting in an artificially high baseline signal in the cerebellum.

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