Differential Distribution of 5Ht<sub>1D</sub>-and 5HT<sub>1B</sub>-Immunoreactivity within the Human Trigemino-Cerebrovascular System: Implications for the Discovery of New Antimigraine Drugs

DOI Web Site 被引用文献1件
  • J Longmore
    Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre Eastwick Road. Harlow, Essex, UK; Department of Neurosurgery, Addenbrooke's Hospital, Cambridge, UK
  • D Shaw
    Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre Eastwick Road. Harlow, Essex, UK; Department of Neurosurgery, Addenbrooke's Hospital, Cambridge, UK
  • D Smith
    Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre Eastwick Road. Harlow, Essex, UK; Department of Neurosurgery, Addenbrooke's Hospital, Cambridge, UK
  • R Hopkins
    Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre Eastwick Road. Harlow, Essex, UK; Department of Neurosurgery, Addenbrooke's Hospital, Cambridge, UK
  • G McAlliste
    Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre Eastwick Road. Harlow, Essex, UK; Department of Neurosurgery, Addenbrooke's Hospital, Cambridge, UK
  • JD Pickard
    Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre Eastwick Road. Harlow, Essex, UK; Department of Neurosurgery, Addenbrooke's Hospital, Cambridge, UK
  • DJS Sirinathsinghji
    Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre Eastwick Road. Harlow, Essex, UK; Department of Neurosurgery, Addenbrooke's Hospital, Cambridge, UK
  • AJ Butler
    Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre Eastwick Road. Harlow, Essex, UK; Department of Neurosurgery, Addenbrooke's Hospital, Cambridge, UK
  • RG Hill
    Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre Eastwick Road. Harlow, Essex, UK; Department of Neurosurgery, Addenbrooke's Hospital, Cambridge, UK

抄録

<jats:p> Sumatriptan, a 5HT<jats:sub>1B/1D</jats:sub>-receptor agonist, is clinically effective as an antimigraine agent. Its therapeutic action may result partly from vasoconstriction of excessively dilated cranial blood vessels (a 5HT<jats:sub>1B</jats:sub>-receptor mediated response). The antimigraine activity of sumatriptan may also result from inhibition of the release of vasoactive neuropeptides from trigeminal sensory fibres within the meninges. The identity of the 5HT<jats:sub>1B/1D</jats:sub>-receptor subtype mediating this effect is unknown. Using 5HT<jats:sub>1D-</jats:sub> and 5HT<jats:sub>1B</jats:sub>-receptor-specific antibodies we have demonstrated a differential distribution of these receptor subtypes within the human trigemino-cerebrovascular system. Only 5HT<jats:sub>1B</jats:sub>-receptor protein was detected on dural arteries. In contrast, only 5HT<jats:sub>1D</jats:sub>-receptor protein was detected on trigeminal sensory neurones including peripheral and central projections to dural blood vessels and to the medulla. Within the medulla 5HT<jats:sub>1D</jats:sub>-receptor protein was confined to discrete areas associated with the trigeminal sensory system. These findings have important implications for the design of new antimigraine drugs. </jats:p>

収録刊行物

  • Cephalalgia

    Cephalalgia 17 (8), 833-842, 1997-12

    SAGE Publications

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