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5-HT7 antagonists: Novel molecules for the unmet migraine prophylaxis market

  • ID: 19775
  • March 2003
  • Lead Discovery
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This report offers a "one stop shop" for personnel involved in the selection, development and commercialization of novel candidates for CNS or cardiovascular disorders, taking readers through multiple aspects of development including target selection/proof of concept, market analysis, the identification of potential competitors and finally an analysis of current pharmaceutical activity in this field. We conclude that 5-HT7 receptor ligands hold considerable potential.

Please view Executive Summary for more details.

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<UL>
<LI>Background
An introduction to the 5-HT receptor family
Expression profile of 5-HT7
Physiological responses to 5-HT7 receptor activation
Circadian system
Sensory processing and hyperalgesia
Smooth muscle function
Potential therapeutic opportunities surrounding 5-HT7 receptor ligands
Sleep disorders
Depression
Schizophrenia
Cardiovascular diseases
Migraine
Epidemiology
Clinical characteristics
The pathophysiology of migraine
Existing treatment options
Acute therapies
Prophylactic treatments
Proof of concept supporting the use of 5-HT7 receptor antagonists for the prophylactic treatment of migraine
</LI>
<LI>Market values
</LI>
<LI>An overview of current development activity
Molecules in development or on the market for the treatment of migraine
Drug profiles
rizatriptan
sumatriptan
naratriptan
almotriptan
zolmitriptan
frovatriptan
eletriptan
dihydroergotamine
arotinolol
alpha-dihydroergocryptine
lomerizine hydrochloride
flunarizine + nicergoline
diclofenac
tolfenamic acid
ibuprofen
indobufen
metergoline
lisuride
metoclopramide+naproxen
domperidone + paracetamol
topiramate
flupirtine
valproate
Trends in the development of anti-migraine treatments
Companies involved in the development of anti-migraine treatments
</LI>
<LI>Patent and development activity surrounding 5-HT7 receptor antagonists
Companies involved in the development of 5-HT7 receptor antagonists
</LI>
<LI>Research tools available for the development of 5-HT7 receptor antagonists
</LI>
<LI>Strategic summary
</LI></UL>

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<P>The migraine market was revolutionized by the launch of the prototypic triptan, sumatriptan in the early 1990's. Due to the high incidence of migraine and its effect on quality of life the highly competitive triptan market is now worth in excess of $2 billion in global sales. The triptans are acute therapies of migraine aborting an attack once it has started rather than preventing it. According to current guidelines 15% of sufferers would benefit from prophylactic treatment however the availability of molecules that effectively prevent migraine attacks with an acceptable tolerability profile is extremely limited. The development of migraine prophylactics therefore represents an unmet clinical need with considerable commercial potential.</P>
<P>Drugs such as the triptans produce cranial vasoconstriction (via activation of 5-HT1B receptors), and inhibition of neuropeptide release from trigeminovascular afferents (via activation of 5-HT1D or 5-HT1F receptors) countering the pathophysiological features of migraine. As well as being able to abort migraine attacks, evidence implicating 5-HT receptors in the etiology of migraine is convincing. Increasing data supports the concept that 5-HT7 receptor activation is responsible for the initial dilatation of cerebral vessels, and the subsequent activation of sensory pathways, consequent neurogenic inflammation around the meningeal vessels, neural sensitization and the activation of pain pathways. </P>
<P>5-HT7 receptor antagonists therefore stand to offer an effective approach to the unmet field of migraine prophylaxis, a finding supported by clinical observations. Additional evidence exists to support the use of antagonists to treat a second unmet market, schizophrenia, while agonists may have therapeutic value in the treatment of cardiovascular disorders and depression. </P>
<P>This report, produced in collaboration with field-leader, José Terrón provides a state of the art of the 5-HT7 receptor, describes the proof of concept supporting its therapeutic potential in relation to these indications and analyzes current pharmaceutical activity surrounding the development of 5-HT7 ligands. Since the primary indication for this class is currently the prophylactic treatment of migraine we provide a full description of this condition. We describe in detail current views on the pathophysiology of migraine, and current migraine treatment options profiling antimigraine treatments on the market or in phase III development. We pay particular attention to studies performed to investigate efficacy and tolerability of existing prophylactics, as well as the role of 5-HT7 in migraine.</P>
<P>Our trend analysis confirms that much of the pharmaceutical activity related to migraine therapeutics remains focussed on abortive therapies and the development of 5-HT7 receptor antagonists able to prevent migraine attacks are therefore unlikely to meet significant competition from other pharmacological classes. We conclude with a description of development activity surrounding 5-HT7 receptor ligands and suggest that although this field is still in its infancy, this situation is expected to soon change.</P>
<P>This report offers a "one stop shop" for personnel involved in the selection, development and commercialization of novel candidates for CNS or cardiovascular disorders, taking readers through multiple aspects of development including target selection/proof of concept, market analysis, the identification of potential competitors and finally an analysis of current pharmaceutical activity in this field. We conclude that 5-HT7 receptor ligands hold considerable potential.
</P>

Note: Product cover images may vary from those shown
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Note: Product cover images may vary from those shown

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