Disease relevance of Almotriptan

• Dose finding, placebo-controlled study of oral almotriptan in the acute treatment of migraine [1].
• CONCLUSIONS: Almotriptan has effects on blood pressure in subjects with controlled hypertension that are consistent with those of other members of the pharmalogic class [2].
• Treatment-emergent adverse events occurred in 15.2% of the subjects in the almotriptan-treated group and in 19.4% in the sumatriptan-treated group (P =.06); treatment-related adverse events occurred in 9.1% and 15.5% of the subjects, respectively (P =.001), including chest pain, which occurred in 0.3% and 2.2%, respectively (P =.004) [3].
• Other symptoms of migraine, including nausea, photophobia and phonophobia, are also alleviated by almotriptan [4].
• Results.-The incidence of nausea, photophobia, and phonophobia at 2 hours after dosing with study medication was significantly reduced (all P <.05) with almotriptan 6.25 mg or 12.5 mg compared with placebo [5].

High impact information on Almotriptan

• Mean changes from baseline during the interval from 0 to 4 hours were 1.59 +/- 3.88, 1.85 +/- 5.94, and 4.84 +/- 5.99 mm Hg for systolic pressure and 1.38 +/- 6.95, 6.25 +/- 9.54, and 11.0 +/- 10.6 mm Hg for diastolic pressure for placebo, 12.5 mg almotriptan, and 25 mg almotriptan, respectively [2].
• OBJECTIVE: Our objective was to investigate the cardiovascular effects of almotriptan, a 5-hydroxytryptamine 1B/1D agonist, in treated patients with hypertension [2].
• OBJECTIVE: To assess the interaction between almotriptan, a 5-HT1B/1D-receptor agonist used to treat migraine, and verapamil, an agent for migraine prophylaxis [6].
• METHODS: Twelve healthy volunteers received the following treatments in a crossover design: (1) 120-mg sustained-release verapamil tablet twice daily for 7 days and one 12.5-mg almotriptan tablet on day 7 and (2) one 12.5-mg almotriptan tablet alone on day 7 [6].
• The pharmacokinetics of almotriptan are linear over a range of oral doses up to 200mg in healthy volunteers [7].

Chemical compound and disease context of Almotriptan

• For the relief of single attacks of migraine, oral almotriptan 12.5mg had similar efficacy to oral sumatriptan 50mg [4].
• Although these data suggest that rizatriptan may be a more effective treatment for migraine than almotriptan, further randomized studies are required to confirm this conclusion [8].
• This study was designed to assess the pharmacokinetics of almotriptan, a 5HT1B/1D agonist used to treat migraine attacks, when administered in the presence and absence of fluoxetine [9].
• Methods: This multicentre, double-blind trial randomized adult migraineurs to almotriptan 12.5 mg (n = 532) or zolmitriptan 2.5 mg (n = 530) for the treatment of a single migraine attack [10].
• We studied the possible cardiovascular effects of single oral doses of 12.5, 25, and 50 mg of almotriptan, a new triptan for treatment of migraine, in a randomized, double-blind, four-way crossover, placebo-controlled study in 24 healthy volunteers aged 18 to 35 years [11].

Biological context of Almotriptan

• Almotriptan is well absorbed after oral administration and the mean absolute bioavailability is 69.1% [7].
• Almotriptan has a favourable pharmacokinetic profile that translates clinically to a rapid onset of action and consistent absorption regardless of age, sex, food intake and status of the acute migraine attack [12].
• Ketoconazole coadministration increased mean almotriptan AUC and Cmax from 312 to 490 ng h/mL and 52.6 to 84.5 ng/mL, respectively [13].
• Almotriptan did not modify blood pressure or heart rate in conscious telemetered normotensive Wistar rats (p.o.), in anaesthetised beagle dogs (i.v.), or in conscious beagle dogs (i.v.), and only produced transient increases when administered (s.c.) to telemetered cynomolgus monkeys [14].
• The disposition kinetics of almotriptan after i.v. and s.c. administration showed biphasic decline described by a two-compartment model [15].

Anatomical context of Almotriptan

• Almotriptan therapy is associated with a low incidence of adverse events, including those affecting the central nervous system and chest [12].
• In ophthalmic arteries the contractile effects of almotriptan and sumatriptan were similar, whereas lower contractile effects were obtained with almotriptan than with sumatriptan in coronary arteries [16].
• In addition, the effects of almotriptan on the pulmonary vein and on bronchial tissues were studied [16].
• Almotriptan showed selectivity of action for migraine-related arteries (i.e. contractile EC(50) of 30 and 700 nm for meningeal and temporal arteries, respectively), whereas the effect on arteries supplying blood to the brain was lower [16].
• A study in anaesthetised cats also demonstrated that almotriptan acts by selectively increasing the resistance of the carotid arteriovenous anastomoses without adversely affecting brain irrigation [17].

Associations of Almotriptan with other chemical compounds

• This paper describes the vascular effects of almotriptan in comparison with sumatriptan in human vessels and tissues in vitro [16].
• The results show that propranolol has no effect on the pharmacokinetics of almotriptan [18].
• Patient satisfaction with treatment response at 2 hours was more than 2-fold greater for rizatriptan (85%) than for almotriptan (68%) (adjusted OR, 2.55; 95% CI, 1.11 to 5.87; P=.03) [8].
• RESULTS: Mean almotriptan AUC was higher (483 +/- 99.9 vs 352 +/- 75.4 ng ml-1 h, P = 0.0001) and oral clearance was lower (26.6 +/- 4.00 vs 36.6 +/- 5.89 l h-1, P = 0.0001) when almotriptan was administered with moclobemide [19].
• Healthy male (n = 3) and female (n = 11) volunteers received (1) 60 mg fluoxetine daily for 8 days and 12.5 mg almotriptan on Day 8 and (2) 12.5 mg almotriptan on Day 8, according to a two-way crossover design [9].

Gene context of Almotriptan

• In addition, different clinical trials conducted to study the effects of CYP3A4, CYP2D6, and MAO-A on the pharmacokinetics of almotriptan confirmed the involvement of these enzymes in the metabolic clearance of this drug and that no dose changes are required in the presence of inhibitors of these enzymes [20].
• Human liver microsomes and S9 fraction metabolize almotriptan by 2-hydroxylation of the pyrrolidine group to form a carbinolamine metabolite intermediate, a reaction catalyzed by CYP3A4 and CYP2D6 [20].
• The use of human liver mitochondria confirmed the contribution of MAO-A to the metabolism of almotriptan [20].
• Almotriptan (LAS 31416) is a new, oral, specific 5-hydroxytryptamine(1B/1D) receptor agonist for the treatment of migraine [21].
• Almotriptan (3-[2-(dimethylamino) ethyl]-5-(pyrrolidin-1-ylsulfonylmethyl)-1H-indole, CAS 154323-57-6) is a new 5-HT1B/1D agonist whose clinical efficacy has been demonstrated in Phase III clinical trials [22].

Analytical, diagnostic and therapeutic context of Almotriptan

• METHODS: Twenty patients with hypertension controlled by medication received the following treatments in a randomized, double-blind, crossover design: one placebo tablet, one 12.5-mg almotriptan tablet, and one 25-mg almotriptan tablet [2].
• Almotriptan plasma concentrations were determined by liquid chromatography-tandem mass spectrometry; urine samples were analyzed by ultraviolet HPLC [6].
• Pain-free status at 2 h postdose is achieved by approximately 39% of patients receiving almotriptan in clinical trials [12].
• A meta-analysis of pooled individual patient data from four randomized, placebo-controlled, double-blind trials comparing several doses of almotriptan (n = 1,908) with placebo (n = 386) was used to investigate the efficacy, speed of onset and tolerability of almotriptan in the acute treatment of migraine [23].
• Plasma and urinary almotriptan concentrations were measured by high-performance liquid chromatography [24].

References