However, there is no evidence as yet that the ability of memantine to protect against extrasynaptic NMDA receptor-mediated excitotoxicity has a disease-modifying effect in Alzheimers, although this has been suggested in animal models.Memantines antagonism on NMDA receptors has aroused interest in repurposing it for mental illnesses such as bipolar disorder, considering the involvement of the glutamatergic system in the pathophysiology of mood disorders. Serotonin
Memantine acts as a non-competitive antagonist at the 5-HT3 receptor, with a potency similar to that for the NMDA receptor. Many 5-HT3 antagonists function as antiemetics, however the clinical significance of this serotonergic activity in the treatment of Alzheimers disease is unknown. Cholinergic
Memantine acts as a non-competitive antagonist at different neuronal nicotinic acetylcholine receptors (nAChRs) at potencies possibly similar to the NMDA and 5-HT3 receptors, but this is difficult to ascertain with accuracy because of the rapid desensitization of nAChR responses in these experiments. It can be noted that memantine is an antagonist at Alpha-7 nAChR, which may contribute to initial worsening of cognitive function during early memantine treatment. Alpha-7 nAChR upregulates quickly in response to antagonism, which could explain the cognitive-enhancing effects of chronic memantine treatment. It has been shown that the number of nicotinic receptors in the brain are reduced in Alzheimers disease, even in the absence of a general decrease in the number of neurons, and nicotinic receptor agonists are viewed as interesting targets for anti-Alzheimer drugs.
Balsalazide is an anti-inflammatory drug used in the treatment of inflammatory bowel disease. It is sold under the brand names Giazo, Colazal in the US and Colazide in the UK. It is also sold in generic form in the US by several generic manufacturers. It is usually administered as the disodium salt. Balsalazide releases mesalazine, also known as 5-aminosalicylic acid, or 5-ASA, in the large intestine. Its advantage over that drug in the treatment of ulcerative colitis is believed to be the delivery of the active agent past the small intestine to the large intestine, the active site of ulcerative colitis. It is in the category of disease-modifying antirheumatic drugs (DMARDs) family of medications. It is unclear exactly how it works. Synthesis
Ex 3 is actually for Ipsalazide. See Ex 4 for Balsalazide proper. Same protocol but uses β-Alanine. Starting material is 4-aminohippuric acid, obtained by coupling para-aminobenzoic acid and glycine. That product is then treated with nitrous acid to give the diazonium salt. Reaction of this species with salicylic acid proceeds at the position para to the phenol to give balsalazide. References
External links
"Balsalazide". Drug Information Portal. U.S. National Library of Medicine.