{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:16:39Z","timestamp":1791090999370,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,1,24]],"date-time":"2014-01-24T00:00:00Z","timestamp":1390521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2014,2]]},"abstract":"Background and Purpose<\/jats:title>The GABAB<\/jats:sub><\/jats:styled-content> 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<\/jats:styled-content>). Here, we tested a novel GABAB<\/jats:sub><\/jats:styled-content> positive allosteric modulator (PAM<\/jats:styled-content>) ADX<\/jats:styled-content>71441 in models of OAB<\/jats:styled-content> in mice and guinea pigs.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>Mice were left untreated or given (p.o.) vehicle (1% CMC<\/jats:styled-content>), ADX<\/jats:styled-content>71441 (1, 3, 10\u2009mg\u2009kg\u22121<\/jats:sup>) or oxybutynin (100\u2009mg\u2009kg\u22121<\/jats:sup>; Experiment 1) or vehicle (1% CMC<\/jats:styled-content>), baclofen (1, 3, 6\u2009mg\u2009kg\u22121<\/jats:sup>) 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<\/jats:styled-content> and the effects of ADX<\/jats:styled-content>71441 (1, 3\u2009mg\u2009kg\u22121<\/jats:sup>) or baclofen (1\u2009mg\u2009kg\u22121<\/jats:sup>), administered i.v., on cystometric parameters were monitored.<\/jats:p><\/jats:sec>Key Results<\/jats:title>In mice, 10\u2009mg\u2009kg\u22121<\/jats:sup> ADX<\/jats:styled-content>71441 increased urinary latencies, reduced the number of urinary events and the total and average urinary volumes. In guinea pigs, ADX<\/jats:styled-content>71441 (1 and 3\u2009mg\u2009kg\u22121<\/jats:sup>) increased the intercontraction interval (ICI<\/jats:styled-content>) and bladder capacity (BC<\/jats:styled-content>), and reduced micturition frequency (MF<\/jats:styled-content>) compared to vehicle. At 3\u2009mg\u2009kg\u22121<\/jats:sup> ADX<\/jats:styled-content>71441 completely inhibited the micturition reflex and induced overflow incontinence in five out of 10 animals. Baclofen slightly increased ICI<\/jats:styled-content> and BC<\/jats:styled-content> and reduced MF<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusion and Implications<\/jats:title>Our findings demonstrate, for the first time, that a GABAB<\/jats:sub> PAM<\/jats:styled-content> has potential as a novel approach for the treatment of OAB<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12517","type":"journal-article","created":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T06:59:35Z","timestamp":1384412375000},"page":"995-1006","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["ADX<\/scp>71441, a novel, potent and selective positive allosteric modulator of the GABAB<\/sub><\/scp> receptor, shows efficacy in rodent models of overactive bladder"],"prefix":"10.1111","volume":"171","author":[{"given":"M","family":"Kalinichev","sequence":"first","affiliation":[{"name":"Addex Therapeutics SA Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Palea","sequence":"additional","affiliation":[{"name":"Facult\u00e9 des Sciences Pharmaceutiques UROsphere Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Haddouk","sequence":"additional","affiliation":[{"name":"Addex Therapeutics SA Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Royer\u2010Urios","sequence":"additional","affiliation":[{"name":"Addex Therapeutics SA Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Guilloteau","sequence":"additional","affiliation":[{"name":"Facult\u00e9 des Sciences Pharmaceutiques UROsphere Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Lluel","sequence":"additional","affiliation":[{"name":"Facult\u00e9 des Sciences Pharmaceutiques UROsphere Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Schneider","sequence":"additional","affiliation":[{"name":"Addex Therapeutics SA Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Saporito","sequence":"additional","affiliation":[{"name":"Melior Discovery Inc. 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