sumatriptan, Imitrex
Role of 5-HT1B/D receptors in canine gastric accommodation: effect of sumatriptan and 5-HT1B/D receptor antagonists.

De Ponti F, Crema F, Moro E, Nardelli G, Frigo G, Crema A.

Department of Pharmacology, University of Bologna, Via Irnerio 48, I-40126 Bologna, Italy. deponti biocfarm.unibo.it

The 5-HT1B/D receptor agonist sumatriptan has been proposed to treat dyspeptic symptoms, because it facilitates gastric accommodation. It is unknown whether stimulation of 5-HT1B/D receptors is involved. Thus, in four conscious dogs, we compared the effects of sumatriptan alone or combined with N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-[1,1-biphenyl]-4-carboxamide hydrocloride (GR-127935), N-[3-[3 (dimethylamino)-ethoxy]-4-methoxyphenyl]-2'-[methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)]-[1,1-biphenyl]-4-carboxamide hydrocloride (SB-216641 hydrochloride), or 3-[4-(4-chloro-phenyl)piperazin-1-yl]-1,1-diphenyl-2-propanol hydrochloride (BRL-15572 hydrochloride) (respectively, nonselective 5-HT1B/D, selective 5-HT1B, and selective 5-HT1D receptor antagonists) on gastric accommodation to isobaric distensions performed with a barostat. An exponential and a linear model were used to fit the pressure-volume relationship. An exponential equation fitted the data better than a linear equation. Sumatriptan (800 nmol/kg iv) induced an immediate gastric relaxation (Deltavolume: 112 +/- 44 ml, P < 0.05). After sumatriptan, the pressure-volume curve was shifted toward significantly higher volumes. This effect was fully reversed by GR-127935 or SB-216641 but not by BRL-15572. In conclusion, 5-HT1B receptors seem to play an important role in modulating gastric accommodation to a distending stimulus. An exponential model for pressure-volume curves fits well with the concept of gastric adaptive relaxation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12646419&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Almotriptan in the treatment of migraine.

Rabasseda X.

Medical Information and Documentation Department, Prous Science, Barcelona, Spain. xrabasseda prous.com

Almotriptan is a new selective serotonin 5-HT(1B/1D) receptor agonist which is chemically related to sumatriptan and is used in the acute treatment of migraine. Almotriptan, like the rest of the triptans, acts by inducing vasoconstriction of the meningeal arteries. The new drug has good oral bioavailability, and in clinical studies has been shown to be at least as effective than sumatriptan 100 mg in alleviating migraine headache and associated symptoms (nausea, vomiting, phonophobia and photophobia) when administered as a single oral dose of 12.5 mg, this being the recommended dose. However, almotriptan has a very good tolerability profile, which has been shown to be superior to that of sumatriptan in two comparative trials. Therefore, almotriptan offers clear advantages over sumatriptan in the acute treatment of migraine attacks. (c) 2001 Prous Science. All rights reserved.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12764423&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Abnormal 5-HT1D receptor function in cluster headache: a neuroendocrine study with sumatriptan.

Pinessi L, Rainero I, Valfre W, Lo Giudice R, Ferrero M, Rivoiro C, Arvat E, Gianotti L, Del Rizzo P, Limone P.

Neurology III, Headache Centre, Department of Neuroscience, Division of Endocrinology, Department of Internal Medicine and Division of Medicine, Department of Internal Medicine, University of Turin, Turin, Italy. lorenzo.pinessi unito.it

The purpose of this study was to assess the sensitivity of 5-HT(1D) receptors in patients with episodic cluster headache using sumatriptan as a pharmacological probe. The drug, a selective 5-HT(1B/1D) agonist, stimulates the secretion of growth hormone and inhibits the release of prolactin, adrenocorticotropic hormone (ACTH) and cortisol. These effects may be used to explore the function of serotonergic systems in vivo. We administered subcutaneous sumatriptan and placebo to 20 patients with cluster headache (10 in the active phase and 10 in the remission period) and to 12 controls. The sumatriptan-induced increase of growth hormone concentrations was significantly (P < 0.05) blunted in patients with active cluster headache. Prolactin and ACTH responses to the drug were significantly (P < 0.05) reduced in patients with cluster headache, both in the active and in the remission period. Our results suggest that cerebral serotonergic functions mediated by 5-HT(1D) receptors are altered in patients with episodic cluster headache.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12780765&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Almotriptan in the treatment of migraine.

Rabasseda X.

Medical Information and Documentation Department, Prous Science, Barcelona, Spain. xrabasseda prous.com

Almotriptan is a new selective serotonin 5-HT(1B/1D) receptor agonist which is chemically related to sumatriptan and is used in the acute treatment of migraine. Almotriptan, like the rest of the triptans, acts by inducing vasoconstriction of the meningeal arteries. The new drug has good oral bioavailability, and in clinical studies has been shown to be as effective or more effective than sumatriptan 100 mg in alleviating migraine headache and associated symptoms (nausea, vomiting, phonophobia and photophobia) when administered as a single oral or subcutaneous dose of 12.5 mg, this being the recommended dose. However, almotriptan has a very good tolerability profile, which has been shown to be superior to that of sumatriptan in a comparative trial. Therefore, almotriptan offers clear advantages over sumatriptan in the acute treatment of migraine attacks. (c) 2001 Prous Science. All rights reserved.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12783094&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Transcranial Doppler in migraine attacks before and after treatment with oral zolmitriptan or sumatriptan.

Thomaides T, Karagounakis D, Spantideas A, Katelanis S.

Neurology Department of Konstandopoulion Complex of Agia Olga General Hospital of Athens, Greece.

BACKGROUND: Intracranial blood flow velocity (BFV) changes in migraine have been studied fairly extensively. Although a number of investigations have been performed in migraineurs with nitroglycerin-induced attacks, there has been no reported transcranial study involving such attack treated with zolmitriptan or sumatriptan. METHODS: With ultrasound, we studied the BFV and pulsatility index (PI) changes in the middle cerebral artery in 45 symptom free, otherwise healthy, unmedicated patients with migraine without aura, and in 15 age- and sex-matched controls before nitroglycerin, at the time of maximum head pain induced by nitroglycerin and every 30 minutes for 2 hours after zolmitriptan (15 subjects) or sumatriptan (15 subjects) administration. Headache was rated on a 4-point scale. RESULTS: During headache attacks, BFV decreased significantly (36.7+/-3.3, 38.4+/-3.4, and 37.4+/-4 cm/sec, respectively, in the zolmitriptan, sumatriptan, and nontreated migraine groups, but not in the controls who were migraine free (P <.01). These abnormalities disappeared 1 hour after zolmitriptan or sumatriptan administration (49.7+/-3.7 and 48.9+/-3.9 cm/sec, respectively). There were no significant changes in PI. CONCLUSION: Our data indicate that nitroglycerin-induced headache in individuals with migraine without aura is associated with BFV changes that are reversed by administration of an oral triptan.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12864759&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Effect of rizatriptan and other triptans on the nausea symptom of migraine: a post hoc analysis.

Lipton RB, Pascual J, Goadsby PJ, Massiou H, McCarroll KA, Vandormael K, Jiang K, Lines CR.

Albert Einstein College of Medicine, Bronx, NY, USA.

OBJECTIVE: To compare the effects of oral rizatriptan, sumatriptan, naratriptan, and zolmitriptan on the relief and emergence of nausea during a migraine attack. METHODS: Data from five randomized, placebo-controlled, double-blind clinical trials in which oral rizatriptan 10 mg was directly compared with oral sumatriptan 100 mg (N = 772), 50 mg (N = 1168), 25 mg (N = 1180), naratriptan 2.5 mg (N = 406), or zolmitriptan 2.5 mg (N = 571) for the acute treatment of a migraine attack were retrospectively analyzed. Migraine was diagnosed according to International Headache Society criteria. Presence or absence of nausea was recorded at baseline and at 0.5, 1, 1.5, and 2 hours after dosing. The end points analyzed were relief of nausea in those who had it at baseline and emergence of nausea in those who were free of it at baseline. Treatments were compared using odds ratios estimated from logistic regression models at 2 hours, and averaged odds ratios for the first 2 hours posttreatment. RESULTS: Approximately 60% of patients in each treatment group had nausea at baseline. In those patients with nausea at baseline, significantly more patients treated with rizatriptan 10 mg were free of nausea at 2 hours compared with sumatriptan 100 mg (66% versus 58%, P =.043), sumatriptan 50 mg (68% versus 57%, P =.010), sumatriptan 25 mg (68% versus 59%, P =.017), and naratriptan 2.5 mg (59% versus 45%, P =.014). Averaging over the four posttreatment time points in the first 2 hours, significantly more patients treated with rizatriptan 10 mg were free of nausea compared with sumatriptan 100 mg (P =.004), sumatriptan 50 mg (P =.001), and naratriptan 2.5 mg (P =.015). No significant differences in nausea relief were seen between rizatriptan 10 mg and zolmitriptan 2.5 mg, either at 2 hours (65% versus 61%, P =.210) or over the first 2 hours (P =.781). Rates of treatment-emergent nausea at 2 hours ranged from 11% to 18% with placebo, from 5% to 13% with rizatriptan 10 mg, and from 10% to 20% with other comparator triptans. CONCLUSIONS: Oral rizatriptan 10 mg was more effective than oral sumatriptan and naratriptan at eliminating nausea within 2 hours in patients who had it at baseline. Rates of emergent nausea in patients who were free of it at baseline were low, and no consistent differences were observed between active treatments.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11576198&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Stability-indicating methods for the determination of sumatriptan succinate.

Bebawy LI, Moustafa AA, Abo-Talib NF.

National Organization for Drug Control and Research (NODCAR), 6 Hussen Kamal el Deen, Ben-el-sariat, Dokki, 12311, Giza, Egyp. gamella is-egypt.com

Four stability-indicating methods were developed for the determination of sumatriptan succinate in the presence of its degradation products. The first method depends on the quantitative densitometric evaluation of thin-layer chromatography of sumatriptan succinate in the presence of its degradation products without any interference. Cyclohexane-dichloromethane-diethylamine (50:40:10 v/v/v) was used as a mobile phase and the chromatogram was scanned at 228 nm. This method determines sumatriptan succinate in the concentration range l-8 microg per spot with mean percentage recovery 100.52+/-1.23%. The second and third methods depend on the use of first-derivative (D(1)) and second-derivative (D(2)) spectrophotometry at 234 and 238 nm, respectively. These methods determine the drug in the concentration range 1.25-10 microg x ml(-1) with mean percentage recovery 99.91+/-1.01% and 99.96+/-1.13% for (D(1)) and (D(2)), respectively. The fourth method depends on the use of ratio derivative spectrophotometric technique. The amplitude in the first derivative of the ratio spectra at 235 nm was selected to determine the cited drug in the presence of its degradation products. Calibration graph is linear in the concentration range 1.25-10 microg x ml(-1) with mean percentage recovery 100.19+/-1.19%. The suggested methods were successfully applied for determining sumatriptan succinate in bulk powder, laboratory-prepared mixtures and pharmaceutical dosage forms (Imigran tablet) with good accuracy and precision. The results obtained by applying the proposed methods were statistically analyzed and compared with those obtained by the reported method.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12907255&dopt=Abstract sumatriptan Imitrex