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Cholinergic Antagonists
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Vishal S. Gulecha, Manoj S. Mahajan, Aman Upaganlawar, Abdulla Sherikar, Chandrashekhar Upasani
Urinary urgency induced by minor inflammatory bladder disorders can be treated by atropine and other muscarinic antagonists. Urinary bladder predominantly consists of M2 and M3 receptors mediating direct activation of contraction of detrusor muscles, especially by M3 receptors subtype. Dicyclomine and oxybutynin are indicated in renal colic and urethral smooth muscle spasm (Sharma and Sharma, 2017; Barar, 2004). Trospium, a nonselective antagonist, is an alternative to oxybutynin. Trospium has better efficacy and reduced side effects than oxybutynin. Darifenacin and solifenacin are other approved agents with enhanced selectivity toward M3 receptors. A directly acting smooth muscle relaxant, flavoxate, possesses anticholinergic and antispasmodic activities and is useful in urinary urge incontinence and for subrapubic pain in cystitis and urethritis (Srivastava, 2017; Sharma and Sharma, 2017).
Urinary Incontinence
Published in David M. Luesley, Mark D. Kilby, Obstetrics & Gynaecology, 2016
Dudley Robinson, Linda Cardozo
Trospium chloride is a quaternary ammonium compound which is non-selective for muscarinic receptor subtypes and shows low biological availability. It crosses the blood-brain barrier to a limited extent and hence would appear to have few cognitive effects.117 A placebo-controlled, randomised, double-blind multicentre trial has shown trospium to increase cystometric capacity and bladder volume at first unstable contraction, leading to significant clinical improvement without an increase in adverse effects over placebo.118 When compared to oxybutynin it was found to have comparable efficacy although was associated with a lower incidence of dry mouth and patient withdrawal.119 At present trospium chloride would appear to be as effective as oxybutynin although it may be associated with fewer adverse effects.
Vive la révolution! a paradigm shift in the pharmacological treatment of schizophrenia
Published in Current Medical Research and Opinion, 2023
Another novel agent in phase 3 of clinical development is a combination of xanomeline and trospium from Karuna Therapeutics, Inc.18. Xanomeline is a muscarinic M1 and M4 receptor agonist and is thought to reduce aberrantly high dopamine signaling to the striatum but is not well tolerated because of peripheral pro-cholinergic adverse effects19,20. These adverse effects can be attenuated with the use of trospium, a muscarinic receptor antagonist that does not cross the blood brain barrier. Prior attempts in the 1950s at using this strategy of combining muscarinic/antimuscarinic medications were limited by the choice of agents available at that time21. This newer approach of combining xanomeline and trospium has been more successful. Xanomeline-trospium combination appears reasonably well-tolerated and demonstrated efficacy for the treatment of schizophrenia in a phase 2 trial of which the results were published in 202122. A recently reported phase 3 trial demonstrated similar results23.
Cognitive and mood side effects of lower urinary tract medication
Published in Expert Opinion on Drug Safety, 2019
A. Elif Muderrisoglu, Klaus F. Becher, Stephan Madersbacher, Martin C. Michel
Adverse effects of muscarinic antagonists as a class are highly plausible mechanistically based on the known function of muscarinic receptors in the CNS [45–47]. Whether such effects occur in a given patient treated with a given drug appears to depend on three factors: the vulnerability of the patients as indicated by permeability of his/her blood-brain-barrier [5] and/or cognitive baseline state; the CNS penetration of the drug [49]; and the subtype-selectivity of the drug. Thus, adverse effects on CNS function can in principle occur with any muscarinic antagonist with oral formulations of oxybutynin apparently having the greatest risk. The only muscarinic antagonist apparently free of that risk is trospium. The latter conclusion is not only based on specific clinical studies [16,19,20,44] but also on the concept that trospium as a quarternary amine does not pass the blood-brain-barrier. The latter has been confirmed in a dedicated study in which oral treatment of elderly volunteers with therapeutic doses of trospium did not result in detectable drug levels in the CNS [50]. These data make trospium the muscarinic antagonist with the smallest potential to disturb CNS function; however, the very same property of being a quarternary amine also causes a limited and highly variable bioavailability [89], which makes prediction of drug exposure in target tissue difficult.
The cognitive safety of antimuscarinics in the treatment of overactive bladder
Published in Expert Opinion on Drug Safety, 2020
George Araklitis, Dudley Robinson
In a randomized, blinded study of 658 older adults (mean age 61 years), comparing trospium chloride with placebo, there was no significant difference in daytime sleepiness or somnolence measured using the Stanford Sleepiness Scale [71]. Adverse events related to the central nervous system were not significantly different between trospium chloride and placebo, at 5.8% and 5.2%, respectively.