Effects of IP-751, Ajulemic Acid, on Bladder Overactivity Induced by Bladder Irritation in Rats

Hiragata, Shiro; Ogawa, Toshihide; Hayashi, Yukio; Tyagi, Pradeep; Seki, Satoshi; Nishizawa, Osamu; Miguel, Fernando de; Chancellor, Michael B.; Yoshimura, Naoki

doi:10.1016/j.urology.2007.02.069

Cited by 44 publications

(38 citation statements)

References 21 publications

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“…Hiragata et al [2007] showed that ajulemic acid, a mixed CB1/CB2 receptor agonist, can suppress normal bladder activity and urinary frequency induced by bladder nociceptive stimuli. The inhibitory effects were inhibited by AM251, a selective CB1 receptor antagonist.…”

Section: Future Directionsmentioning

confidence: 99%

Prospective pharmacologic therapies for the overactive bladder

Andersson

2009

Therapeutic Advances in Urology

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Lower urinary tract symptoms (LUTS), overactive bladder syndrome (OAB) and detrusor overactivity (DO) are all conditions that can have major effects on quality of life and social functioning. Antimuscarinic drugs are first-line treatment-they often have good initial response rates, but adverse effects and decreasing efficacy cause long-term compliance problems, and alternatives are needed. The recognition of the functional contribution of the urothelium, the spontaneous myocyte activity during bladder filling, and the diversity of nerve transmitters has sparked interest in both peripheral and central modulation of LUTS/OAB/DO pathophysiology. There may be several new possibilities to treat LUTS/OAB/DO. 3 -AR agonists (YM178), PDE 5 inhibitors (sildenafil, tadalafil, vardenafil), vitamin D analogs (elocalcitol), combinations ( 1 -AR antagonist þ antimuscarinic), and drugs with a central mode of action (tramadol, aprepitant) all have Randomized controlled trial (RCT) documented efficacy. Which of these therapeutic principles will be developed to clinically useful treatments remains to be established.

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Section: Future Directionsmentioning

confidence: 99%

Prospective pharmacologic therapies for the overactive bladder

Andersson

2009

Therapeutic Advances in Urology

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“…Cystometric studies supporting the role of cannabinoids on efferent functions have shown that CB agonists increased micturition threshold and voiding interval [12][13][14]. A study by Walczak et al.…”

Section: Introductionmentioning

confidence: 99%

Cannabinoid receptor expression in the bladder is altered in detrusor overactivity

et al. 2015

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Introduction:Immunohistochemical (IHC) evidence shows cannabinoid receptors (CB) are expressed in human bladders and cannabinoid agonists are known to inhibit detrusor contractility. However, the mechanism for this inhibition remains unknown. In addition, the role of CB in detrusor overactivity (DO) is under investigated. The aim of this study was to compare CB expression in normal and DO human bladders and to further characterise these receptors.

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“…Cystometric studies have shown an increase of the micturition threshold in rats receiving systemic cannabinoids in normal and inflamed conditions induced by acetic acid, cyclophosphamide or turpentine oil [66,67]. These effects were stronger when the cannabinoids were administered through a close-arterial route rather than systemically through the tail vein of the rat, supporting the hypothesis of a local regulatory role of the cannabinoid system in the micturition reflex [67].…”

Section: Cannabinoid Receptor Function In the Urinary Bladdermentioning

confidence: 80%

“…The mechanism by which cannabinoid receptors could modulate this reflex is by the presence of CB 1 receptors in the afferent nerve fibre endings located in the suburothelial layer, which is supported by in vitro studies where CB 1 agonists reduce neuronal activity and attenuate bladder contractility as a result of electrical field stimulation in isolated mouse bladder strips [61,68]. In rats, anandamide, WIN 55212-2 (synthetic CB non-selective agonist), and Ajulemic acid (IP-751) (synthetic THC analogue), suppress normal bladder activity and the urinary frequency induced by bladder irritation suggesting the inhibitory effects are least in part mediated by CB 1 receptors [66,67,69]. A recent study, showed that CB 2 receptor mediated signals using a high affinity CB 2 receptor selective agonist, cannabinor 3.0 mg/kg, increased the micturition intervals and volumes by 52% (p <0.05) and 96% (p<0.01), respectively, and increased threshold and flow pressures by 73% (p<0.01) and 49% (p<0.001), respectively, in conscious rats during cystometry [1].…”

Section: Cannabinoid Receptor Function In the Urinary Bladdermentioning

confidence: 94%

Cannabinoids and the Urinary Bladder

Bakali¹

2013

Gynecol Obstet

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The presence of the Endocannabinoid System (ECS) in the urinary bladder has led to speculation that endocannabinoid-signalling is involved in the signal transduction pathways regulating bladder relaxation and may be involved in pathophysiological processes of the bladder. On the basis of this evidence, it was postulated that the binding of endocannabinoids to the cannabinoid receptors (CB 1 and CB 2 ) may result in relaxation of the urinary bladder during the filling phase. Dysregulation of the ECS in human bladder may be responsible for the aetiopathogenesis of Overactive Bladder Syndrome (OAB) and Detrusor Overactivity (DO).

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Effects of IP-751, Ajulemic Acid, on Bladder Overactivity Induced by Bladder Irritation in Rats

Cited by 44 publications

References 21 publications

Prospective pharmacologic therapies for the overactive bladder

Prospective pharmacologic therapies for the overactive bladder

Cannabinoid receptor expression in the bladder is altered in detrusor overactivity

Cannabinoids and the Urinary Bladder

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