Rizatriptan

Sample preparation Condition a 1 mL 100 mg Bond Elut C2 SPE cartridge with two 1 mL portions of MeOH and two 1 mL portions of water. Mix 1 mL plasma with 100 xL 100 ng/mL IS in water, add to the SPE cartridge, wash with 1 mL water, wash with two 1 mL portions of MeOHrwater 30 70, elute with 1 mL MeOH 10 mM pH 5.0 ammonium acetate 60 40. Evaporate the eluate to dryness at 50°, reconstitute the residue with 200 xL mobile phase, sonicate for 10 min, vortex, inject a 25 p,L aliquot. 

Mobile phase MeCN MeOH water trifluoroacetic acid 54 4 42 0.1 

Detector MS, PE Sciex API-Ill triple quadrupole, nebulizer probe 500°, positive ionization, nebulizer gas at 80 psi, auxiliary gas at 2 L/min, corona discharge -1-3 xA, 0.1143 mm orifice, orifice 45 V, collision gas argon, m/z 270-201 

McLoughlin, DA. Olah, T.V. Ellis, J.D. Gilbert, J.D. Halpin, RA. Qusintitation of the 5HTid agonists MK-462 and sumatriptan in plasma by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry, J.Chromatogr.A, 1996, 726, 115-124. 

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C2H4N4 584-13-4) see Rizatriptan benzoate 7(R)-amino-3-[(l,2,3-triazoI-4-ylthio)methyl]-3-cephem-4-carboxylic acid... 

CjiHisNO So 3285-33-4) see Tiotixene dimethy laminothioacetamide (C4Hh)N2S 27507-2S-4) see Nizatidine 4>dimethylamino-l-trimethylsUyl-l-butanone (CyH2tNOSi) see Rizatriptan benzoate (3p,17p)-7,17-dimethylandrast-5-enc-3,7,17-triol (C21H34O4 96613-61-5) see Calusterone dimethylaniline... 

ClI 7790-99-0) see Bunamiodyl locetamic acid lopamidol lopanoic acid lophenoic acid lotalamic acid Rizatriptan benzoate... 

C25H42N40Si2 160194-32-1) see. Rizatriptan benzoate 2, 5-tri-O-benzoyl-a-D-ribofuranosyl acetate (C28H24O9 70832-64-3) see Stavudine... 

QHijOjP 122-52-1) see Foscamet sodium Gesirinone 7-O-triethylsilylbaccatin III (C,7H520 Si 115437-21-3) see Paclitaxel 4-triethylsilyl 3-butyn-l-ol triethylsilyl ether (C 4Hj40Si2 160194-28-5) see Rizatriptan benzoate triethylsilyl chloride... 

Direct attenuation of the excitability of neurons in the trigeminal nuclei, as 5-HTib/ 5-HTid receptors on pain transmission neurons in the trigeminal nucleus caudalis and in the upper cervical cord, are activated. Stimulation of these receptors is caused by second-generation triptans that cross the blood-brain barrier such as zolmitriptan, naratriptan, rizatriptan and eletriptan. 

Rizatriptan Oral tablets, 5, 10 5-10 2 hours Ergot derivatives ... 

The P-blockers propranolol and timolol are FDA-approved for migraine prophylaxis, but other drugs in the class are also as effective.46 Cautious dosage titration is advised for those patients who do not have other indications for P-blocker use. Rizatriptan interacts with propranolol and thus dosages must be titrated downward, or another triptan chosen for abortive therapy.36 Comorbid reactive airway disease is a relative contraindication to P-blocker prophylaxis, and patients with cardiac conduction disturbances should be closely monitored. Calcium channel antagonists are often used when patients cannot tolerate P-blockers. They are purported to beneficially... 

The drug discovery route to rizatriptan (1) began with the preparation of 1-(4 -nitrobenzyl)-l,2,4-triazole 5 using 4-nitrobenzyl bromide (4) and 1,2,4-triazole. (Scheme 4.1). Benzylation of the sodium salt of 1,2,4-triazole prepared with NaH was not regioselective and afforded a 1.5 1 mixture of l-(4 -nitrobenzyl)-1,2,4-triazole (5) and its regioisomer, 4-(4 -nitrobenzyl)-l,2,4-triazole. The desired isomer 5 was isolated in 52% yield after silica gel chromatography. Hydrogenation... 

Though the medicinal chemistry route allowed for the preparation of rizatriptan (1) in a straightforward manner, it suffered from several shortcomings that prohibited implementation of the synthesis on a kilogram scale ... 

Scheme 4.4 Application of the improved Fisher indole synthesis for rizatriptan.

Rizatriptan (Maxalt ) A 5-HTm Receptor Agonist 4.1.2.2 Palladium-Catalyzed Indole Synthesis... 

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