History
The synthesis of trospium was described by scientists from Dr. Robert Pfleger Chemische Fabrik GmbH,  Heinz Bertholdt, Robert Pfleger, and Wolfram Schulz, in US. Pat. No. 3,480,626 (the US equivalent to DE119442), and its activity was first published in the literature in 1967.The first regulatory approval was granted in Germany in August 1999 to Madaus AG for Regurin 20 mg Tablets. : 13  Madaus is considered the originator for regulatory filings worldwide. The German filing was recognized throughout Europe under the Mutual Recognition Procedure. : 13 Madaus licensed the US rights to trospium chloride to Interneuron in 1999 and Interneuron ran clinical trials in the US to win FDA approval. Interneuron changed its name to Indevus in 2002 Indevus entered into a partnership with Odyssey Pharmaceuticals, a subsidiary of Pliva, to market the drug in April 2004, and won FDA approval for the drug, which it branded as Sanctura, in May 2004. The approval earned Indevus a milestone payment of $120M from Pliva, which had already paid Indevus $30 million at signing; the market for overactive bladder therapies was estimated to be worth $1.1 billion in 2004. In 2005 Pliva exited the relationship, selling its rights to Esprit Pharma, and in September 2007 Allergan acquired Esprit, and negotiated a new agreement with Indevus under which Allergan would completely take over the US manufacturing, regulatory approvals, and marketing. A month before, Indevus had received FDA approval for an extended release formulation that allowed once a day dosing, Sanctura XR.
Medical uses
Trospium chloride is used for the treatment of overactive bladder with symptoms of urge incontinence and frequent urination.It shouldnt be used with people who retain urine, who have severe digestive conditions, myasthenia gravis, narrow-angle glaucoma, or tachyarrhythmia.It should be used in caution with people who have problems with their autonomous nervous system (dysautonomia) or who have gastroesophageal reflux disease, or in whom fast heart rates are undesirable, such as people with hyperthyroidism, coronary artery disease and congestive heart failure.Trospium chloride is rated Pregnancy Category C, as there are no adequate and well-controlled studies of trospium chloride in pregnant women and there were signs of harm to the fetus in animal studies. The drug was excreted somewhat in the milk of nursing mothers. The drug was studied in children. Side effects
Side effects are typical of gastrointestinal effects of anticholinergic drugs, and include dry mouth, indigestion, and constipation. These side effects lead to problems with adherence, especially for older people. The only CNS side effect is headache, which was very rare. Tachycardia is a rare side effect. Mechanism of action
Trospium chloride is a muscarinic antagonist. Trospium chloride blocks the effect of acetylcholine on muscarinic receptors organs that are responsive to the compounds, including the bladder. Its parasympatholytic action relaxes the smooth muscle in the bladder. Receptor assays showed that trospium chloride  has negligible affinity for nicotinic receptors as compared to muscarinic receptors at concentrations obtained from therapeutic doses. Pharmacokinetics
After oral administration, less than 10% of the dose is absorbed.