Innovative drug development for headache disorders

by Olesen, Jes; Ramadan, Nabih

• ISBN13: 9780199552764
• ISBN10: 0199552762
• Edition: 1st
• Format: Hardcover
• Copyright: 2008-11-01
• Publisher: Oxford University Press

Summary

Migraine treatment improved considerably with the advent of the 'triptans' in the 1990s. While the drugs used previously for headache treatment had efficacy, some compounds had bothersome side effects and their overuse could lead to severe complications. In the early days of the triptans, itwas widely presumed that migraine was no longer a treatment problem. However, it has gradually been recognized that a significant proportion of patients are not responsive to triptans or do not tolerate them. It is now clear that, even with effective treatment, patients with frequent migraineattacks are not treated well exclusively with acute medications. This is partly because patients are still bothered by the attacks and partly because frequent intake of acute medication may result in medication-overuse headache. These problems have led to a renewed interest in preventive migrainedrugs. Part of the Frontiers in Headache Research series, this book summarizes the several promising new avenues for the development of future drugs for the treatment of migraine, including cortical-spreading depression inhibition, nitric oxide synthase inhibition and calcitonin gene-related peptide (CGRP)receptor antagonism, as well as other potential targets. The book presents frontline knowledge of these evolving modalities as far as it is available in the public domain. It is hoped that readers and their patients will find it exciting to learn about all the novel possibilities, and also that theimpressive research advances in migraine will lead to increased funding, not only of migraine but also of other types of headache.

Table of Contents

Screening models

Bolette Christiansen

The human GABA transporter GAT-2 - From cloning to high throughput screening

Low throughput preclinical models for headache

Human models - screening models

Trials methodology

Stricter success criteria, qualitative and quantitative end points: Acute vs. prevention trials

Health related quality of life and similar end points

Clinically relevant designs and outcome measures for acute migraine trials

Effectiveness of different steroid dosage in Tolosa-Hunt syndrome with different phenotypes: some critical points about the new HIS classification

Discussion summary: Trials methodologyNO and spreading depression modulators

Inducible nitric oxide synthase and development of new migraine treatments

Mechanisms of cortical spreading depression as targets for migraine therapy

Tonabersat

Discussion Summary: NO and spreading depression modulatorsCGRP and 5-HT modulators

Calcitonin gene-related peptide (CGRP): relevance for migraine

New 5-HT related drug targets

Effect of two novel CGRP-binding compounds in a closed cranial window rat model

Vasoactive intestinal polypeptide is unlikely to be a target for headache and migraine treatment

Discussion Summary: CGRP and 5-HT modulatorsIon Channel modulators and antiepileptics

Migraine: from genes to pathophysiology - transgenic mouse models of migraine

Katp channels and migraine

Antiepileptic drugs and migraine

Discussion Summary: Ion channel modulators and antiepilepticsOther future targets for headache therapy

Innovative drug development for headache disorders - Glutamate

The modulation of TRPV1 channels by cannabinoid1 receptors

Future targets for headache therapy: Prostanoids

Role of anandamide in the modulation of nitroglycerin-induced hyperalgesia - a study in the rat

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