[color=blue]Eur J Pharmacol. 2002 Mar 29;439(1-3):83-92.
Arvanil-induced inhibition of spasticity and persistent pain: evidence for therapeutic sites of action different from the vanilloid VR1 receptor and cannabinoid CB(1)/CB(2) receptors.
Brooks JW, Pryce G, Bisogno T, Jaggar SI, Hankey DJ, Brown P, Bridges D, Ledent C, Bifulco M, Rice AS, Di Marzo V, Baker D.
Pain Research Group, Department of Anaesthetics, Faculty of Medicine, Imperial College, Chelsea and Westminster Hospital Campus, London, UK.
Activation of cannabinoid receptors causes inhibition of spasticity, in a mouse model of multiple sclerosis, and of persistent pain, in the rat formalin test. The endocannabinoid anandamide inhibits spasticity and persistent pain. It not only binds to cannabinoid receptors but is also a full agonist at vanilloid receptors of type 1 (VR1). We found here that vanilloid VR1 receptor agonists (capsaicin and N-N'-(3-methoxy-4-aminoethoxy-benzyl)-(4-tert-butyl-benzyl)-urea [SDZ-249-665]) exhibit a small, albeit significant, inhibition of spasticity that can be attenuated by the vanilloid VR1 receptor antagonist, capsazepine. Arvanil, a structural "hybrid" between capsaicin and anandamide, was a potent inhibitor of spasticity at doses (e.g. 0.01 mg/kg i.v.) where capsaicin and cannabinoid CB(1) receptor agonists were ineffective. The anti-spastic effect of arvanil was unchanged in cannabinoid CB(1) receptor gene-deficient mice or in wildtype mice in the presence of both cannabinoid and vanilloid receptor antagonists. Likewise, arvanil (0.1-0.25 mg/kg) exhibited a potent analgesic effect in the formalin test, which was not reversed by cannabinoid and vanilloid receptor antagonists. These findings suggest that activation by arvanil of sites of action different from cannabinoid CB(1)/CB(2) receptors and vanilloid VR1 receptors leads to anti-spastic/analgesic effects that might be exploited therapeutically.
PMID: 11937096 [PubMed - indexed for MEDLINE]
[color=blue]Urologe A. 2006 Oct;45(10):1283-8.
[Intravesical treatment of overactive bladder syndrome]
[Article in German]
Haferkamp A, Hohenfellner M.
Urologische Klinik, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. Axel_Haferkamp@med.uni-heidelberg.de
Overactive bladder and urgency incontinence are common conditions generally treated with oral anticholinergic medication. Despite the development of new antimuscarinic substances, many patients are refractory to or cannot tolerate the oral therapy due to severe side effects. Intravesical instillation therapy can provide an alternative method to manage detrusor overactivity. Intravesical instillation of anticholinergics such as oxybutynin and trospium chloride can achieve cholinergic blockade without producing systemic side effects. Botulinum toxin type A injections into the detrusor have been shown to increase bladder capacity and to decrease detrusor overactivity for 6 or more months. Intravesical local anesthetics such as lidocaine and bupivacaine block the conduction of unmyelinated C fibers which results in an increase of functional bladder capacity. Intravesical capsaicin and resiniferatoxin also affect the afferent C fiber innervation of the bladder, leading to a decrease in detrusor overactivity and also an increased bladder capacity. The use of intravesical anticholinergics and of local anesthetic medications, both known for their short-term efficacy, is limited due to the necessity of daily intermittent catheterization. In conclusion, intravesical therapies can provide an alternative treatment for the management of overactive bladder.
PMID: 16972089 [PubMed - indexed for MEDLINE]
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