sumatriptan, Imitrex
Tolfenamic acid decreases migraine recurrence when used with sumatriptan.

Krymchantowski AV, Adriano M, Fernandes D.

Centro de Avaliacao e Tratamento da dor de Cabeca do Rio de Janeiro, Brazil.

Although sumatriptan is an effective drug for the treatment of acute migraine attacks, recurrence has been cited as an important limitation for its use. Tolfenamic acid is also effective in the acute treatment of migraine attacks. We studied the recurrence rate of migraine attacks with the use of sumatriptan plus tolfenamic acid among patients who presented frequent recurrence with sumatriptan. Fifty migraineurs were retrospectively studied, all having treated at least 10 attacks with 100 mg P.O.; sumatriptan was effective in at least eight of them. The patients also presented recurrence in less than 24 h in at least five of the treated attacks. We then used sumatriptan 100 mg plus tolfenamic acid 200 mg P.O. during the first 60 min of the attack; 240 attacks were treated and there was recurrence in 57 (23.8%). With sumatriptan alone, 5 out of 8 attacks (62.5%) presented recurrence. We therefore conclude that the combination sumatritpan plus tolfenamic acid is effective in reducing the recurrence rate from 5 of 8 (62.5%) to 1.19 of 5 (23.8%). Further prospective studies with a double-blind design and a higher number of treated attacks are necessary to confirm these initial observations.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10234467&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Antinociceptive effect of sumatriptan in mice.

Jain NK, Kulkarni SK.

Pharmacology Division, Panjab University, Chandigarh, India.

Antinociceptive effect of the antimigraine drug sumatriptan (5-HT1A agonist) was studied against acetic acid-induced writhing in mice. Sumatriptan produced the effect in a dose-dependent manner (1, 5, 10 and 20 mg/kg, s.c.). Naloxone (1 mg/kg i.p.) an opiate antagonist failed to reverse sumatriptan-induced antinociception. Cholinomimetic physostigmine (0.05 mg/kg, i.p.) potentiated and the muscarinic antagonist atropine (5 mg/kg, i.p.) blocked the antinociceptive effect of sumatriptan, respectively. The antinociceptive effect of sumatriptan was compared with an another 5-HT agonist (5-HT1A) buspirone which also produced antinociception. Like sumatriptan-analgesia, the buspirone response was also potentiated by physostigmine in atropine sensitive way. Further, buspirone potentiated the analgesic effect of sumatriptan. These observations suggest that 5-HT1A agonists produce antinociception possibly by modulating central cholinergic activity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10356959&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Investigation of the role of 5-HT1B and 5-HT1D receptors in the sumatriptan-induced constriction of porcine carotid arteriovenous anastomoses.

De Vries P, Willems EW, Heiligers JP, Villalon CM, Saxena PR.

Department of Pharmacology, Dutch Migraine Research Group and Cardoivascular Research Institute, COEUR, Erasmus University Medical Centre Rotterdam, The Netherlands.

1. It has previously been shown that the antimigraine drug sumatriptan constricts porcine carotid arteriovenous anastomoses via 5-HT1-like receptors, identical to 5-H1B/1D receptors. The recent availability of silent antagonists selective for the 5-HT1B (SB224289) and 5-HT1D (BRL15572) receptor led us to further analyse the nature of receptors involved. 2. In pentobarbitone-anaesthetized, bilaterally vagosympathectomized pigs, sumatriptan (30, 100 and 300 microg kg(-1), i.v.) dose-dependently decreased carotid arteriovenous anastomotic conductance by up to 70+/-5%. 3. The dose-related decreases in carotid arteriovenous anastomotic conductance by sumatriptan (30, 100 and 300 microg kg(-1), i.v.) remained unchanged in animals treated (i.v.) with 1 mg kg(-1) of BRL15572 (maximum decrease: 72+/-3%), but were significantly attenuated by 1 mg kg(-1) (maximum decrease: 30+/-11%) and abolished by 3 mg kg(-1) (maximum decrease: 3+/-7%) of SB224289. The highest dose of SB224289 did not attenuate the hypertension, tachycardia or increases in carotid blood flow induced by bolus injections of noradrenaline (0.1-3 microg kg(-1), i.v.). 4. The results indicate that sumatriptan constricts porcine carotid arteriovenous anastomoses primarily via 5-HT1B, but not via 5-HT1D receptors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10385240&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Effect of sumatriptan on external pancreatic secretion and its interaction with endogenous norepinephrine in the rat.

Nagain-Domaine C, Presset O, Chariot J, Roze C.

INSERM U410, Faculte de Medecine Xavier Bichat, Paris, France.

We reported previously that blocking norepinephrine reuptake by nisoxetine could modulate external pancreatic secretion in the rat. We report in this study the interaction of serotonin (5-HT) with endogenous catecholamines by using sumatriptan, an agonist of 5-HT1 receptors, in combination with nisoxetine. Urethane-anesthetized male Wistar rats were fitted with an acute pancreatic fistula. Nisoxetine (0.3 mg/kg, i.v.) and sumatriptan (0.1-1 mg/kg, s.c.) were administered alone or in combination. Pancreatic secretion was measured under stimulation by 2-deoxy-D-glucose (2DG; 75 mg/kg, i.v.), by vagal electrical stimulation (4 V, 2 ms, 10 Hz), or by acetylcholine (60-1,800 microg/kg.h). (i) 2DG: Nisoxetine alone inhibited 2DG-induced pancreatic secretion (p < 0.01). Sumatriptan alone also produced a dose-related inhibition of 2DG-induced pancreatic secretion (p < 0.01). When sumatriptan and nisoxetine were combined, protein response to 2DG remained inhibited, whereas water and electrolyte secretion was restored. (ii) Vagal stimulation: Nisoxetine did not modify water and electrolyte output in response to vagal electrical stimulation (VES), whereas it inhibited protein response by 75%. Sumatriptan alone strongly inhibited pancreatic response to VES (p < 0.01). When nisoxetine and sumatriptan were combined, the protein response to VES remained inhibited, whereas water and electrolyte response to VES was restored. (iii) Acetylcholine: Nisoxetine and sumatriptan alone or combined did not modify pancreatic response to acetylcholine. These results indicate that noradrenergic and serotonergic agents can indirectly affect pancreatic secretion through a modulation of the vagal cholinergic pathway. Nisoxetine and sumatriptan interact negatively on hydroelectrolytic pancreatic secretion, whereas they inhibit the secretion of enzymes both alone and in combination.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10416693&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Sumatriptan and ergotamine overuse and drug-induced headache: a clinicoepidemiologic study.

Evers S, Gralow I, Bauer B, Suhr B, Buchheister A, Husstedt IW, Ringelstein EB.

Department of Neurology, University of Munster, Germany.

Drug-induced headache, particularly ergotamine-induced headache, is a common problem in migraine treatment. Some case reports suggest that even the new serotonergic antimigraine drugs such as sumatriptan can lead to overuse and subsequent drug-induced headache. We performed a controlled study to identify the rate of sumatriptan overuse and sumatriptan-induced headache and compared it to the rate of ergotamine overuse and ergotamine-induced headache. Two thousand sixty-five consecutive heachache patients, all experienced in intake of sumatriptan (n = 631) or ergotamine (n = 620), were enrolled over a three-year study period. The rates of overuse and drug-induced headache and the clinical features of the subgroups were compared. Risk factors for sumatriptan overuse were identified. The rates of ergotamine and sumatriptan overuse were 14.2% and 3.5%, respectively (p < 0.001). Drug-induced headache could be found more frequently in cases of ergotamine overuse than in cases of sumatriptan overuse (68% versus 32%; p < 0.01). Development of sumatriptan overuse was most common in patients with previous drug-induced headache (68%), combined headache as the primary headache type (45%), and subcutaneous application of sumatriptan (45%). We conclude that sumatriptan intake can lead to overuse and subsequent drug-induced headache. The risk for overuse and drug-induced headache is significantly lower than in patients with ergotamine intake. This might be caused in part by the relatively short period of sumatriptan availability on the market. The new generation of serotonin-1B/D-receptor agonists in the treatment of headache should have a potential for overuse similar to that of traditional headache drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10442248&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Headache medication-use among primary care headache patients in a health maintenance organization.

Von Korff M, Black LK, Saunders K, Galer BS.

Center for Health Studies, Group Health Cooperative of Puget Sound, Seattle, WA 98101, USA.

OBJECTIVE: Medication-use among headache patients 2 and 5 years after a primary care headache visit is assessed, and the pattern of medication-use compared before and after the introduction of subcutaneous sumatriptan among migraineurs. SETTING AND PATIENTS: The study was carried out among headache patients visiting a primary care physician at the Group Health Cooperative of Puget Sound in 1989-90. METHODS: We report medication-use patterns 2 and 5 years later for the 530 subjects completing both a 2-year (1991-92) and a 5-year (1994-95) follow-up interview. Medication-use was determined by self-report for the month prior to the interview. Medication-use to control or prevent headache is shown for all headache patients and for those meeting International Headache Society criteria for migraine at the 2-year and the 5-year follow-up. RESULTS: The overall pattern of medication-use was similar at the 2-year and the 5-year follow-up, before and after the introduction of subcutaneous sumatriptan (March, 1993). There was a modest but statistically significant decline in the use of opioid and sedative-hypnotic medications, and in the use of ergotamine. At 5 years, 11% of migraineurs reported use of sumatriptan in the prior month. The large majority of study patients used symptomatic medications, usually non-prescription analgesics, sedative-hypnotics, and opiates. Only one-fifth of the migraineurs reported use of a prophylactic medication for headache. CONCLUSIONS: Continuing use of symptomatic headache medications was characteristic of patients with migraine and other common forms of headache. The introduction of subcutaneous sumatriptan was not associated with notable change in this pattern, although a modest reduction in use of sedative-hypnotics and opiates was observed. Overall, the pattern of use of headache medications was similar before and after the introduction of subcutaneous sumatriptan.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10448544&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
5-Hydroxytryptamine(1F) receptors do not participate in vasoconstriction: lack of vasoconstriction to LY344864, a selective serotonin(1F) receptor agonist in rabbit saphenous vein.

Cohen ML, Schenck K.

Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA. cohenml lilly.com

Recently, several novel approaches to the treatment of migraine have been advanced, including selective 5-hydroxytryptamine (or serotonin) 1B/1D (5-HT(1B/1D)) receptor agonists such as sumatriptan and 5-HT(1F) receptor agonists such as LY344864. Many 5-HT(1B/1D) receptor agonists have been identified based on their ability to produce cerebral vascular contraction, whereas LY344864 was identified as an inhibitor of trigeminal nerve-mediated dural extravasation. In our study, several triptan derivatives were compared with LY344864 for their ability to contract the rabbit saphenous vein, a tissue used in the preclinical identification of sumatriptan-related agonists. Sumatriptan, zolmitriptan, rizatriptan, and naratriptan all contracted the rabbit saphenous vein from baseline tone, whereas LY344864 in concentrations up to 10(-4) M did not contract the rabbit saphenous vein. Furthermore, vascular contractions to sumatriptan were markedly augmented in the presence of prostaglandin F(2alpha) (PGF(2alpha)). However, even in the presence of PGF(2alpha) (3 x 10(-7) M), LY344864 did not contract the rabbit saphenous vein in concentrations well in excess of its 5-HT(1F) receptor affinity (pK(i) = 8.2). Only when concentrations exceeded those likely to activate 5-HT(1B) and 5-HT(1D) receptors (>10(-5) M) did modest contractile responses occur in the presence of PGF(2alpha). Use of these serotonergic agonists revealed a significant correlation between the contractile potency in the rabbit saphenous vein and the affinities of these agonists at 5-HT(1B) and 5-HT(1D) receptors, although contractile agonist potencies were not quantitatively similar to 5-HT(1B) or 5-HT(1D) receptor affinities. In contrast, no significant correlation existed between the contractile potencies of these serotonergic agonists in the rabbit saphenous vein and their affinity at 5-HT(1F) receptors. These data support the contention that activation of 5-HT(1F) receptors will not result in vascular contractile effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10454462&dopt=Abstract sumatriptan Imitrex