CGRP is believed to cause sensitization of trigeminal nociceptive neurons, contributing to the pain experienced in migraine.Sumatriptan is also shown to decrease the activity of the trigeminal nerve, which presumably accounts for sumatriptans efficacy in treating cluster headaches. The injectable form of the drug has been shown to abort a cluster headache within 30 minutes in 77% of cases. Pharmacokinetics
Sumatriptan is administered in several forms: tablets, subcutaneous injection, and nasal spray. Oral administration (as succinate salt) has low bioavailability, partly due to presystemic metabolism—some of it gets broken down in the stomach and bloodstream before it reaches the target arteries. A rapid-release tablet formulation with the same bioavailability but a high concentration can achieve therapeutic effects on average 10–15 minutes earlier than other oral forumulations. When injected, sumatriptan is faster-acting (usually within 10 minutes), but the effect lasts for a shorter time. Sumatriptan is metabolised primarily by monoamine oxidase A into 2-{5-[(methylsulfamoyl)methyl]-indole-3-yl}acetic acid, which is then conjugated to glucuronic acid. These metabolites are excreted in the urine and bile. Only about 3% of the active drug may be recovered unchanged. There is no simple, direct relationship between sumatriptan concentration (pharmacokinetics) per se in the blood and its anti-migraine effect (pharmacodynamics). This paradox has, to some extent, been resolved by comparing the rates of absorption of the various sumatriptan formulations, rather than the absolute amounts of drug that they deliver. History
In 1991, Glaxo received approval for sumatriptan, which was the first available triptan. In July 2009, the US FDA approved a single-use jet injector formulation of sumatriptan.
It is indicated for the treatment of inborn errors in primary bile-acid synthesis due to 3β-hydroxy-Δ5-C27-steroid oxidoreductase deficiency or Δ4-3-oxosteroid-5β-reductase deficiency in infants, children and adolescents aged one month to 18 years and adults.Cholic acid FGK (Kolbam) was approved for medical use in the European Union in November 2015. It is indicated for the treatment of inborn errors of primary bile acid synthesis, in infants from one month of age for continuous lifelong treatment through adulthood, encompassing the following single enzyme defects:
sterol 27-hydroxylase deficiency (presenting as cerebrotendinous xanthomatosis, CTX);
2- (or alpha-) methylacyl-CoA racemase (AMACR) deficiency;
cholesterol 7 alpha-hydroxylase (CYP7A1) deficiency.The most common side effects include peripheral neuropathy (nerve damage in the hands and feet), diarrhea, nausea (feeling sick), acid reflux (stomach acid flowing up into the mouth), esophagitis (inflammation of the food pipe), jaundice (yellowing of the skin and eyes), skin problems (lesions) and malaise (feeling unwell). Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. References
External links
"Cholic acid". Drug Information Portal. U.S. National Library of Medicine.