Almotriptan

Molecular formula C17H25N3O2S Molecular weight 335.47 CAS Registry No 154323-57-6 Merck Index 13,301 

Sample preparation Condition a C2 SPE cartridge (Baker) with 2 mL MeCN and 2 mL water. Dilute 500 lL plasma or 100 iL urine with 1 mL water containing IS, mix, add to the SPE cartridge, wash with 750 iL MeCNrwater 30 70, wash with 250 aL water, elute with mobile phase over 1 min (straight onto column ( )). 

Guard column Guardpak [xBondapak CN Column 150 x 4 5 (xm Spherisorb ODS-2 

Mobile phase MeCN 50 mM pH 4.0 sodium phosphate bufifer triethylamine 20 80 0.2 Flow rate 1 Detector UV 227 

Internal standard 4 [3-(2-aminoethyl)-lH-indol-5-yhnethylsulfonyl]piperazine-l-car- 

---

Almotriptan 6,25 or 12,5 mg at onset can repeat after 2 hours if needed Optimal dose is 12.5 mg maximum daily dose is 25 mg... 

Sumatriptan, zolmitriptan, naratriptan, rizatriptan, almotriptan, fro-vatriptan, and eletriptan are appropriate first-line therapies for patients with moderate to severe migraine or as rescue therapy when nonspecific medications are ineffective. 

Not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. Safety and efficacy have not been established for cluster headache, which is present in an older, predominantly male population (almotriptan, eletriptan, frovatriptan, sumatriptan tablets and spray, zolmitriptan). 

ALMOTRIPTAN Doses of 6.25 and 12.5 mg were effective for the acute treatment of migraines in adults, with the 12.5 mg dose tending to be a more effective dose. Individuals may vary in response to doses of almotriptan therefore, individualize the dosage. 

Hepatic function impairment- The maximum decrease expected in the clearance of almotriptan caused by hepatic impairment is 60%. Therefore, do not exceed the maximum daily dose of 12.5 mg over a 24-hour period, and use a starting dose of 6.25 mg. 

Pharmacology Naratriptan, rizatriptan, sumatriptan, frovatriptan, almotriptan, eletriptan, and zolmitriptan are selective agonists for a vascular 5-hydroxytryptamine-i(serotonin) receptor subtype. Use of 5-HT- agonists results in... 

Lactation Sumatriptan and eletriptan are excreted in breast milk. Zolmitriptan, naratriptan, almotriptan, frovatriptan, and rizatriptan are excreted in rat milk. Children Safety and efficacy in children have not been established. 5-HT- receptor... 

Corneal opacities Sumatriptan, eletriptan, naratriptan, and almotriptan cause corneal opacities and defects in dogs, raising the possibility that these changes may occur in humans. 

Drugs that may be affected by itraconazole include alfentanil, almotriptan, alprazolam, amphotericin B, aripiprazole, benzodiazepines, buspirone, busulfan, calcium blockers, carbamazepine, cilostazol, cisapride, corticosteroids, cyclosporine, digoxin, disopyramide, docetaxel, dofetilide, eletriptan, epierenone, ergot alkaloids, haloperidol, HMG-CoA reductase inhibitors, hydantoins (phenytoin), hypoglycemic agents, oral midazolam, phosphodiesterase type 5 inhibitors, pimozide, polyenes, protease inhibitors, quinidine, rifamycins, sirolimus, tacrolimus, tolterodine, triazolam, trimetrexate, vinca alkaloids, warfarin, and zolpidem. 

Sumatriptan was the first compound in the pharmacological class of the triptans, followed by zolmitriptan, naratriptan, rizatriptan, almotriptan, frovatriptan and eletriptan. It can offer rapid relief. Theoretically, triptans should only be given at the moment of the aura (accentuation of the vasoconstriction and aggravation of the neurological signs). 

Take a single dose of almotriptan as soon as migraine symptoms appear... 

USAN Almotriptan malate Trade Name Axerl Company Almirall/Janssen Launched 2001 M.W. 335.47... 

Scheme 21. Synthesis of almotriptan (5) using the Grandberg modification of the Fischer indole reaction.

Almotriptan has also been synthesized via decarboxylation of the carboxylic acid intermediate 65, but a detailed preparation of 65 was not provided in the patent literature (Scheme 22)." The patent indicates that the carboxy indole 65 was prepared according to the method of Gonzalez.°° Thus, (2-oxo-tetrahydro-3-furanyl)-glyoxylic acid ethyl ester (62) was heated in aqueous H2SO4 to give 2-oxo-5-hydroxypentanoic acid in situ, which was treated with hydrazine 59 to produce hydrazone 63. Fischer cyclization of 63 using HCl gas in DMF gave the lactone 64, which was converted to carboxylic acid 65. Decarboxylation of 65 was catalyzed by cuprous oxide in quinoline at 190 °C to afford almotriptan (5)." ... 

Lastly, a formal synthesis of almotriptan (5) has been published by the Bosch group in Spain using an intramolecular Heck approach (Scheme 23). lodination of aniline 58 with bis(pyridine)iodonium(I) tetrafluoroborate followed by reaction with trifluoroacetic anhydride (TFAA) gave the o-iodotrifluoroacetanilide 66. Alkylation of 66 with methyl 4-bromocrotonate afforded 67, which underwent palladium catalyzed... 

Heck cyclization with concomitant deprotection of the trifluoroacetyl group to form the indoleacetic methyl ester 68. Compound 68 was hydrolyzed and then treated with PCI5 followed by dimethylamine to give the amide 69, which was reduced with LiAlHi to afford almotriptan (5). 

Almotriptan (Axert) Aspirin Butalbital Compound (Fiorinal)... 

---