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Nociceptin/Orphanin FQ and Urinary Bladder.
Patrizia Angelico1, Marco Barchielli2, Massimo Lazzeri3
1Pharmaceutical R&D Division, Recordati S.p.A., Milan, Italy. angelico.p@recordati.it.
Handbook of Experimental Pharmacology
|November 16, 2018
Summary
Nociceptin/orphanin FQ (N/OFQ) and its derivative Rec 0438 show promise for treating overactive bladder by inhibiting the micturition reflex. Intravesical administration of these NOP receptor agonists effectively manages bladder function without developing tolerance.
Area of Science:
- Pharmacology
- Urology
- Neuroscience
Background:
- Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the NOP receptor.
- N/OFQ modulates various biological functions, including the micturition reflex.
Purpose of the Study:
- To investigate the potential of NOP receptor agonists for treating overactive bladder.
- To evaluate the efficacy and safety of Rec 0438, a novel NOP full agonist.
Main Methods:
- Administration of N/OFQ and Rec 0438 via intravesical instillation.
- Assessment of effects on rat micturition reflex and urodynamic parameters in patients.
- Evaluation of tolerance liability after repeated treatment.
Main Results:
- N/OFQ and Rec 0438 demonstrated robust inhibitory effects on rat micturition.
- Intravesical N/OFQ increased bladder capacity and volume threshold in overactive bladder patients.
- Rec 0438 showed high potency, selectivity, and long-lasting action without tolerance development after 2 weeks of treatment.
Conclusions:
- NOP receptor agonists, including Rec 0438, are effective in managing the micturition reflex.
- Intravesical administration of NOP agonists offers a promising therapeutic strategy for overactive bladder.
- Rec 0438 represents a potential innovative drug for overactive bladder treatment.
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