Ambenonium is a cholinesterase inhibitor with all the pharmacologic actions of acetylcholine, both the muscarinic and nicotinic types. It was marketed under the brand name Mytelase, but was withdrawn from the market in the United States in 2010. Ambenonium, similar to pyridostigmine and neostigmine, is used for the treatment of muscle weakness and fatigue in people with myasthenia gravis.Ambenonium exerts its actions against myasthenia gravis by competitive, reversible inhibition of acetylcholinesterase. The disease myasthenia gravis occurs when the body inappropriately produces antibodies against acetylcholine receptors, and thus inhibits proper acetylcholine signal transmission (when acetylcholine binds to acetylcholine receptors of striated muscle fibers, it stimulates those fibers to contract). Ambenonium reversibly binds acetylcholinesterase at the anionic site, which results in the blockage of the site of acetycholine binding, thereby inhibiting acetylcholine hydrolysis and enhancing cholinergic function through the accumulation of acetycholine at cholinergic synpases. In turn this facilitates transmission of impulses across the myoneural junction and effectively treats the disease.

Laquinimod is a new orally available carboxamide derivative, which is currently developed for relapsing remitting (RR) and chronic progressive (CP) forms of multiple sclerosis (MS; RRMS or CPMS) as well as neurodegenerative diseases. The mechanism of action of laquinimod is not fully elucidated because the molecular target is not known. Treatment with laquinimod led to a significant and persistent increase in brain-derived neuroprotective factor (BDNF) serum levels compared to placebo treatment. In human studies, a decrease of pro-inflammatory and an increase of anti-inflammatory cytokines have been measured. After commercial launch the unexpected severe cardiac adverse events (AEs) such as serositis, pericarditis, and myocardial infarction were detected.

Levomethadyl acetate (LAAM) is a synthetic opioid agonist with actions qualitatively similar to morphine (a prototypic mu agonist) and affecting the central nervous system (CNS) and smooth muscle. Principal actions include analgesia and sedation. Tolerance to these effects develops with repeated use. An abstinence syndrome generally occurs upon cessation of chronic administration similar to that observed with other opiates, but with slower onset, more prolonged course, and less severe symptoms. LAAM exerts its clinical effects in the treatment of opiate abuse through two mechanisms. First, LAAM cross-substitutes for opiates of the morphinetype, suppressing symptoms of withdrawal in opiate-dependent individuals. Second, chronic oral administration of LAAM can produce sufficient tolerance to block the subjective “high” of usual doses of parenterally administered opiates. Since the introduction of levomethadyl in 1995, the manufacturer has received increasing reports of severe cardiac-related adverse events, including QT interval prolongation, Torsades de Pointes and cardiac arrest. Other cardiac-related adverse events have also been reported, including arrhythmias, syncope, and angina. These events led to the removal of levomethadyl from the European market in March 2001. A very small number of patients may benefit from levomethadyl, but the risk of continued distribution and use no longer outweighs the overall benefits.

levomethadone, or R-(−)-methadone, is the active enantiomer of methadone; having approximately 50x the potency of the S-(+)-enantiomer as well as greater μ-opioid receptor selectivity.

Distigmine is an acetylcholinesterase (AChE) inhibitor. Distigmine shows direct binding to muscarinic receptors in the rat bladder, and repeated oral administration of distigmine causes downregulation of muscarinic receptors in the rat bladder. The observed direct interaction of distigmine with the bladder muscarinic receptors may partly contribute to the therapeutic and/or side effects seen in the treatment of detrusor underactivity. It is usually used to treat myasthenia gravis, dysuria due to hypotonic bladder such as neurogenic bladder or after surgery. Common side effects are: nausea/vomiting, abdominal pain, diarrhea, increased salivation, hypersecretion in respiratory tract, sweating, bradycardia, miosis, difficulty in breathing. Distigmine has a greater risk of causing cholinergic crisis because of accumulation of the drug being more likely than with neostigmine or pyridostigmine and so distigmine is rarely used as a treatment for myasthenia gravis, unlike pyridostigmine and neostigmine.

Subarachnoid haemorrhage (SAH) following cerebral aneurysm rupture or trauma can result in the induction of secondary ischaemic brain damage via a decrease in microvascular perfusion, a disruption of the blood-brain barrier and consequent vasogenic oedema, and the delayed spasm of the major cerebral arteries (i.e. vasospasm). It is increasingly apparent that oxygen radical-induced, iron-catalyzed lipid peroxidation (LP) within the subarachnoid blood and vascular wall plays a key role in the occurrence of these secondary events. Tirilazad mesylate, is a nonglucocorticoid, 21-aminosteroid, is a potent cytoprotective inhibitor of LP that works by a combination of radical scavenging and membrane stabilizing properties. It has been demonstrated to attenuate the acute and delayed vascular consequences of SAH and to protect the brain against ischaemic insults. Tirilazad mesylate has been proposed to treat acute ischaemic stroke. When tested on animal models, tirilazad protects brain tissue, and reduces brain damage. However, the drug fails to treat, and even worsens a stroke when studied on a human being.

Acetylleucine is a drug that is used for symptomatic treatment of acute vestibular vertigo and dizziness. Its pharmacodynamics are not fully understood. The hypothesis is that it restores the membrane potential, via an interaction with membrane phospholipids on the injured side of vestibular neurons mainly in the thalamus or parietal region of the cortex. Clinical trials on animals showed an improvement in locomotor balance after forced rotation or unilateral vestibular neurotomy. Acetylleucine has a marketing authorisation in France although there is no evidence of its efficacy on human. Acetylleucine neither reduced the nausea associated with this provocative stimulus, nor hastened the acquisition or retention of vestibular habituation of motion sickness and nystagmus.

Xaliproden is an orally active 5HT1-A receptor antagonist that was being developed by Sanofi. It has been evaluated for the treatment of Alzheimer's disease and amyotrophic lateral sclerosis (ALS), and protection against peripheral neurotoxicity associated with certain cancer chemotherapies. Two large, 18-month, clinical trials of xaliproden (monotherapy or adjunctive therapy, respectively) in patients with mild to moderate AD (MMSE, 16–26, inclusive) were completed in 2007. Failure to demonstrate sufficient efficacy in both trials resulted in cancelation of the xaliproden development program for AD in September 2007.

Choline alfoscerate (alpha-Glycerylphosphorylcholine or Alpha-GPC) is a nootropic choline-containing phospholipid. Choline alphoscerate increases the release of acetylcholine in rat hippocampus, facilitates learning and memory in experimental animals, improves brain transduction mechanisms and decreases age-dependent structural changes occurring in rat brain areas involved in learning and memory. The compound exerts neuroprotective effects in models of altered cholinergic neurotransmission and of brain vascular injury. In clinical studies choline alphoscerate improved memory and attention impairment, as well as affective and somatic symptoms in dementia disorders. In Europe alpha-GPC is a prescription medication for the treatment of Alzheimer's disease. It is available in two forms; one is taken by mouth, and the other is given as a shot. In the United States alpha-GPC is only available as a dietary supplement, mostly in products promoted to improve memory. Other uses for alpha-GPC include treatment of various kinds of dementia, stroke, and "mini-stroke" (transient ischemic attack, TIA). Alpha-GPC is also used for improving memory, thinking skills, and learning.

Flunarizine is a selective calcium entry blocker with calmodulin binding properties and histamine H1 / dopamine D2 blocking activity. It is not available in the US but marketed in other countries for prophylaxis of a migraine, occlusive peripheral vascular disease, the vertigo of central and peripheral origin, motion sickness and as an adjuvant in the therapy of epilepsy. The drug is also investigated for the treatment of schizophrenia.