Dexmecamylamine (TC-5214, also known, as S isomer of mecamylamine) is a positive allosteric modulator of α4β2 neuronal nicotinic receptors, rather than an open-channel blocker. It was evaluated as a potential adjunct treatment for patients with major depressive disorder (MDD). TC-5214 was generally well tolerated, however, the studies were not supportive of an antidepressant effect for TC-5214 in patients with MDD and inadequate response to prior antidepressant therapy. The Phase 2b clinical trial of TC-5214 for the treatment for overactive bladder (OAB) revealed the high dose of TC-5214 demonstrated mixed results on the co-primary endpoints by providing a statistically significant reduction in micturition frequency and an improvement that did not reach statistical significance on episodes of urinary incontinence. As a consequence of these results, this drug was discontinuing further development of TC-5214 in OAB. The study for using TC-5214 in patients with refractory hypertension was also terminated.

Gisadenafil is a phosphodiesterase V inhibitor in clinical development at Pfizer. It had been in phase II clinical trials for the treatment of Benign prostatic hyperplasia; Chronic obstructive pulmonary disease; Erectile dysfunction; Overactive bladder. Treatment-emergent adverse events were: headache, myalgia, dyspepsia, back pain.

Cizolirtine is a potent analgesic in mice and rats, with an efficacy superior to that of aspirin and other nonsteroid anti-inflammatory drugs. Recent studies have shown that the analgesic effect of cizolirtine could be related, at least partially, to an inhibition of spinal substance P and calcitonin gene-related peptide release. Cizolirtine has been in clinical trials for the treatment of pain and overactive bladder. Reported adverse events are: dry mouth, dizziness, nausea, vomiting, blurred vision.

Propantheline is an antimuscarinic agent used for the treatment of excessive sweating (hyperhidrosis), cramps or spasms of the stomach, intestines (gut) or bladder, and involuntary urination (enuresis). It can also be used to control the symptoms of irritable bowel syndrome and similar conditions. Propantheline is one of a group of antispasmodic medications which work by blocking the action of the chemical messenger acetylcholine, which is produced by nerve cells, to muscarinic receptors present in various smooth muscular tissues, in places such as the gut, bladder, and eye. Normally, the binding of acetylcholine induces involuntary smooth muscular contractions. Varying degrees of drying of salivary secretions may occur as well as decreased sweating. Ophthalmic side effects include blurred vision, mydriasis, cycloplegia, and increased ocular tension. Other reported adverse reactions include urinary hesitancy and retention, tachycardia, palpitations, loss of the sense of taste, headache, nervousness, mental confusion, drowsiness, weakness, dizziness, insomnia, nausea, vomiting, constipation, bloated feeling, impotence, suppression of lactation, and allergic reactions or drug idiosyncrasies including anaphylaxis, urticaria and other dermal manifestations.

Succinic acid is a dicarboxylic acid, which has multiple biological roles as a metabolic intermediate being converted into fumarate by the enzyme succinate dehydrogenase in complex 2 of the electron transport chain which is involved in making ATP, and as a signaling molecule reflecting the cellular metabolic state. Succinate is generated in mitochondria via the tricarboxylic acid cycle (TCA), an energy-yielding process shared by all organisms. Succinate can exit the mitochondrial matrix and function in the cytoplasm as well as the extracellular space, changing gene expression patterns, modulating epigenetic landscape or demonstrating hormone-like signaling. Dysregulation of succinate synthesis, and therefore ATP synthesis, happens in some genetic mitochondrial diseases, such as Leigh's disease, and Mela's disease and degradation can lead to pathological conditions, such as malignant transformation, inflammation and tissue injury. Succinic acid is a precursor to some polyesters and a component of some alkyd resins. Succinic acid also serves as the bases of certain biodegradable polymers, which are of interest in tissue engineering applications. As a food additive and dietary supplement, succinic acid is generally recognized as safe by the U.S. Food and Drug Administration. Succinic acid is used primarily as an acidity regulator in the food and beverage industry. It is also available as a flavoring agent, contributing a somewhat sour and astringent component to umami taste.[11] As an excipient in pharmaceutical products, it is also used to control acidity or as a counter ion. Drugs involving succinate include metoprolol succinate, sumatriptan succinate, Doxylamine succinate or solifenacin succinate.

Succinic acid is a dicarboxylic acid, which has multiple biological roles as a metabolic intermediate being converted into fumarate by the enzyme succinate dehydrogenase in complex 2 of the electron transport chain which is involved in making ATP, and as a signaling molecule reflecting the cellular metabolic state. Succinate is generated in mitochondria via the tricarboxylic acid cycle (TCA), an energy-yielding process shared by all organisms. Succinate can exit the mitochondrial matrix and function in the cytoplasm as well as the extracellular space, changing gene expression patterns, modulating epigenetic landscape or demonstrating hormone-like signaling. Dysregulation of succinate synthesis, and therefore ATP synthesis, happens in some genetic mitochondrial diseases, such as Leigh's disease, and Mela's disease and degradation can lead to pathological conditions, such as malignant transformation, inflammation and tissue injury. Succinic acid is a precursor to some polyesters and a component of some alkyd resins. Succinic acid also serves as the bases of certain biodegradable polymers, which are of interest in tissue engineering applications. As a food additive and dietary supplement, succinic acid is generally recognized as safe by the U.S. Food and Drug Administration. Succinic acid is used primarily as an acidity regulator in the food and beverage industry. It is also available as a flavoring agent, contributing a somewhat sour and astringent component to umami taste.[11] As an excipient in pharmaceutical products, it is also used to control acidity or as a counter ion. Drugs involving succinate include metoprolol succinate, sumatriptan succinate, Doxylamine succinate or solifenacin succinate.

Succinic acid is a dicarboxylic acid, which has multiple biological roles as a metabolic intermediate being converted into fumarate by the enzyme succinate dehydrogenase in complex 2 of the electron transport chain which is involved in making ATP, and as a signaling molecule reflecting the cellular metabolic state. Succinate is generated in mitochondria via the tricarboxylic acid cycle (TCA), an energy-yielding process shared by all organisms. Succinate can exit the mitochondrial matrix and function in the cytoplasm as well as the extracellular space, changing gene expression patterns, modulating epigenetic landscape or demonstrating hormone-like signaling. Dysregulation of succinate synthesis, and therefore ATP synthesis, happens in some genetic mitochondrial diseases, such as Leigh's disease, and Mela's disease and degradation can lead to pathological conditions, such as malignant transformation, inflammation and tissue injury. Succinic acid is a precursor to some polyesters and a component of some alkyd resins. Succinic acid also serves as the bases of certain biodegradable polymers, which are of interest in tissue engineering applications. As a food additive and dietary supplement, succinic acid is generally recognized as safe by the U.S. Food and Drug Administration. Succinic acid is used primarily as an acidity regulator in the food and beverage industry. It is also available as a flavoring agent, contributing a somewhat sour and astringent component to umami taste.[11] As an excipient in pharmaceutical products, it is also used to control acidity or as a counter ion. Drugs involving succinate include metoprolol succinate, sumatriptan succinate, Doxylamine succinate or solifenacin succinate.

Besipirdine is a potential novel first-in-class oral treatment for over active bladder currently in Phase II development, with a mechanism of action clearly different from that of antimuscarinics. It was under evaluation by Aventis up to phase III for Alzheimer’s disease, involving the administration of the compound to over 1500 patients. However, this research has been discontinued. Besipirdine antagonizes alpha-2 and alpha-1 adrenoceptors and inhibits both norepinephrine and serotonin uptake. The most common adverse events were asymptomatic postural hypotension and asymptomatic bradycardia.

Propiverine is a well established antimuscarinic agent. It’s indicated in adults for the symptomatic treatment of urinary incontinence and/or increased urinary frequency and urgency in patients with overactive bladder syndrome or neurogenic detrusor overactivity (detrusor hyperreflexia) from spinal cord injuries, e.g. transverse legion paraplegia. As well as blocking muscarinic receptors in the detrusor muscle, the drug also inhibits cellular calcium influx, thereby diminishing muscle spasm. Overdose with the muscarinic receptor antagonist propiverine hydrochloride can potentially result in central anticholinergic effects, e.g. restlessness, dizziness, vertigo, disorders in speech and vision and muscular weakness. Moreover, severe dryness of mucosa, tachycardia and urinary retention may occur.