The non-peptide neurokinin1 receptor antagonist, RP 67580, blocks neurogenic plasma extravasation in the dura mater of rats

Authors

  • Sara L. Shepheard,

    1. Department of Pharmacology, Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex
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  • David J. Williamson,

    1. Department of Pharmacology, Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex
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  • Raymond G. Hill,

    1. Department of Pharmacology, Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex
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  • Richard J. Hargreaves

    1. Department of Pharmacology, Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex
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Abstract

A non-peptide neurokinin1 (NK1) receptor antagonist, RP 67580, that is selective for the rodent subtype of the NK1 receptor, dose-dependently reduced plasma extravasation in the dura mater produced by electrical stimulation of the trigeminal ganglion in rats, with an ID50 of 0.6 μg kg−1. Its enantiomer RP 68651 was some 400 fold less active. The results indicate that neurogenic plasma extravasation within the dura mater is NK1 receptor-mediated and suggest that NK1 receptor antagonists may have a role as antimigraine agents.

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