Although the prevalence of overactive bladder (OAB) is similar in both male and female populations, females have a greater tendency to seek medical advice regarding their symptoms. A review of the evidence of therapy among women shows that a variety of modalities has been shown to be effective for symptom improvement in women with OAB. Bladder retraining/re-education should be considered for all women with OAB. With respect to first-line pharmacotherapy with antimuscarinic agents, the development of extended release preparations, bladder selective M3 antagonists and alternative routes of delivery, have improved compliance and persistence. Other pharmacotherapeutic options with potential for providing benefit include antidepressants, vasopressin analogues, alpha-adrenoceptor antagonists and beta-adrenoceptor agonists. There are also a number of newer agents currently being investigated, including calcium channel blocking agents, potassium channel opening drugs, beta agonists and neurokinin receptor antagonists. Intravesical injections of botulinum toxin may be an alternative, while surgery can be considered for truly intractable cases.

01 Dec 2009·Expert Opinion on Investigational DrugsQ2 · MEDICINE

Tachykinin receptor antagonists in clinical trials

Q2 · MEDICINE

Review

Author: Carlo A Maggi ; Stefano Evangelista ; Laura Quartara ; Maria Altamura

Tachykinins (TKs) are small peptides widely distributed in the central and peripheral nervous systems where they act as neurotransmitters. Potent and selective TKs antagonists have been developed in the last 20 years and many efforts have been made to prove their efficacy in the treatment of various diseases. Herein the most prominent results in the clinical development are reported and discussed. For aprepitant, the only compound of this class to have been launched to date, results of clinical studies and postmarketing cost-effectiveness data for the treatment of chemotherapy-induced emesis are discussed. The field is still well active, as currently proof-of-concept studies for indications initially missed (i.e., depression) are ongoing and new targets are under investigation.

01 May 2009·Current Pharmaceutical DesignQ4 · MEDICINE

Tachykinin Receptors as Therapeutic Targets in Stress-Related Disorders

Q4 · MEDICINE

Review

Author: Ebner, Karl ; Sartori, Simone B. ; Singewald, Nicolas

The first report demonstrating the therapeutic efficacy of an orally applied neurokinin-1 (NK1) receptor antagonist in depression was published 10 years ago. Although there were difficulties to reproduce this particular finding, a huge amount of data has been published since this time, supporting the potential therapeutic value of various tachykinin ligands as promising novel tools for the management of stress-related disorders including anxiety disorders, schizophrenia and depression. The present review summarizes evidence derived from anatomical, neurochemical, pharmacological and behavioral studies demonstrating the localization of tachykinin neuropeptides including substance P (SP), neurokinin A, neurokinin B and their receptors (NK1, NK2, NK3) in brain areas known to be implicated in stress-mechanisms, mood/anxiety regulation and emotion-processing; their role as neurotransmitters and/or neuromodulators within these structures and their interactions with other neurotransmitter systems including dopamine, noradrenaline and serotonin (5-hydroxytryptamine, 5-HT). Finally, there is clear functional evidence from animal and human studies that interference with tachykinin transmission can modulate emotional behavior. Based on these findings and on evidence of upregulated tachykinin transmission in individuals suffering from stress-related disorders, several diverse tachykinin receptor antagonists, as well as compounds with combined antagonist profile have been developed and are currently under clinical investigation revealing evidence for anxiolytic, antidepressant and antipsychotic efficacy, seemingly characterized by a low side effect profile. However, substantial work remains to be done to clarify the precise mechanism of action of these compounds, as well as the potential of combining them with established and experimental therapies in order to boost efficacy.

100 Deals associated with M3 receptor antagonists( Università di Camerino)

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