ArticleBritish journal of pharmacology2014
ADX71441, a novel, potent and selective positive allosteric modulator of the GABA(B) receptor, shows efficacy in rodent models of overactive bladder.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 29 citations in OpenAlex.
- Normalization of network activity in an epilepsy model with a constitutively active GABBR2 variant.Brain : a journal of neurology · 2026Article
- Article
- Psychiatric History and Overactive Bladder Symptom Severity in Ambulatory Urogynecological Patients.Journal of clinical medicine · 2021Article
- Effects of Dietary Vitamin E Supplementation in Bladder Function and Spasticity during Spinal Cord Injury.Brain sciences · 2018Article
- The GABANeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
- The Metabotropic Glutamate Receptor 4 Positive Allosteric Modulator ADX88178 Inhibits Inflammatory Responses in Primary Microglia.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2016Article
- Netupitant, a Potent and Highly Selective NK1 Receptor Antagonist, Alleviates Acetic Acid-Induced Bladder Overactivity in Anesthetized Guinea-Pigs.Frontiers in pharmacology · 2016Article
- GABABritish journal of pharmacology · 2015Article
- Activation of the γ-Aminobutyric Acid Type B (GABA(B)) Receptor by Agonists and Positive Allosteric Modulators.Journal of medicinal chemistry · 2015Review
- Role of principal ionotropic and metabotropic receptors in visceral pain.Journal of neurogastroenterology and motility · 2015Article
- Discovery of a Negative Allosteric Modulator of GABAB Receptors.ACS medicinal chemistry letters · 2014Article
- Reduction of excessive alcohol drinking by a novel GABAB receptor positive allosteric modulator ADX71441 in mice.Psychopharmacology · 2014Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe GABAB receptor agonist baclofen reduces urethral resistance and detrusor overactivity in patients with spasticity. However, baclofen's side effects limit its use for the treatment of overactive bladder (OAB). Here, we tested a novel GABAB positive allosteric modulator (PAM) ADX71441 in models of OAB in mice and guinea pigs. EXPERIMENTAL APPROACH: Mice were left untreated or given (p.o.) vehicle (1% CMC), ADX71441 (1, 3, 10 mg kg(-1) ) or oxybutynin (100 mg kg(-1) ; Experiment 1) or vehicle (1% CMC), baclofen (1, 3, 6 mg kg(-1) ) or oxybutynin (Experiment 2). Treated mice were then overhydrated with water, challenged with furosemide, before being placed into micturition chambers and monitored for urinary parameters. In anaesthetized guinea pigs, intravesical infusion of acetic acid was used to induce OAB and the effects of ADX71441 (1, 3 mg kg(-1) ) or baclofen (1 mg kg(-1) ), administered i.v., on cystometric parameters were monitored. KEY
resultsIn mice, 10 mg kg(-1) ADX71441 increased urinary latencies, reduced the number of urinary events and the total and average urinary volumes. In guinea pigs, ADX71441 (1 and 3 mg kg(-1) ) increased the intercontraction interval (ICI) and bladder capacity (BC), and reduced micturition frequency (MF) compared to vehicle. At 3 mg kg(-1) ADX71441 completely inhibited the micturition reflex and induced overflow incontinence in five out of 10 animals. Baclofen slightly increased ICI and BC and reduced MF. CONCLUSION AND IMPLICATIONS: Our findings demonstrate, for the first time, that a GABAB PAM has potential as a novel approach for the treatment of OAB.
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