sumatriptan, Imitrex
Activation of sensory nerves in guinea-pig isolated basilar artery by nicotine: evidence for inhibition of trigeminal sensory neurotransmission by sumatriptan.

O'Shaughnessy CT, Connor HE.

Pharmacology 2 Department, Glaxo Research & Development Ltd., Ware, Herts, UK.

Nicotine (100 microM), but not electrical field stimulation or potassium chloride (0.1-3 microM), caused capsaicin (1 microM)- and tetrodotoxin (1 microM)-sensitive relaxations of guinea-pig isolated basilar artery precontracted with prostaglandin F2 alpha. Nicotine-induced responses were blocked by the neurokinin NK1 receptor antagonist, GR82334 (10 microM), but were unaffected by the calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP-(8-37) (1 microM). This suggests that nicotine activates capsaicin-sensitive sensory nerves in guinea-pig basilar artery to cause relaxation predominantly via substance P release. The vascular 5-HT1 receptor agonist, sumatriptan (0.3 and 3 microM), inhibited nicotine-induced relaxation (by 50 and 80% respectively); the inhibitory effect of sumatriptan (0.3 microM) was attenuated in the presence of the non-selective 5-HT1 receptor antagonist, methiothepin (0.1 microM). These data suggest that sumatriptan can inhibit sensory neurotransmission in guinea-pig basilar artery via activation of inhibitory prejunctional 5-HT1 receptors on sensory nerve terminals.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7957591&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
A novel 5-HT receptor or a combination of 5-HT receptor subtypes may mediate depression of a spinal monosynaptic reflex in vitro.

Crick H, Manuel NA, Wallis DI.

Department of Physiology, University of Wales, Cardiff, U.K.

The monosynaptic reflex (MSR), recorded in vitro from the neonatal rat spinal cord, was depressed by 5-hydroxytryptamine (5-HT) and 5-HT receptor agonists. The results, together with our previous findings, indicate an apparent rank order of potency: 5-carboxamidotryptamine (5-CT) > sumatriptan > methysergide > 5-HT >> 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) > 5-methoxytryptamine (5-MeOT) = 1-[3-(trifluoromethyl)phenyl]-piperazine (TFMPP) > alpha-methyl-5-hydroxytryptamine (alpha-Me 5-HT) >> (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). The equipotent molar ratios were 5-CT 0.12, sumatriptan 0.4, methysergide 0.72, 5-HT 1.0, 8-OH-DPAT 13.3, 5-MeOT 26.7, TFMPP 31, alpha-Me 5-HT 402 and DOI > 3333. Time for peak depression from start of agonist application was 3-4 min for 5-HT, 5 min for sumatriptan and 5-MeOT, 5-7 min for alpha-Me 5-HT and 12 min for 8-OH-DPAT. The half-time for recovery from peak depression was 1.5 +/- 0.3 min for 5-HT, 2.8 +/- 0.3 min for 5-MeOT, 5.3 +/- 1.5 min for sumatriptan, 13 +/- 2.9 min for 8-OH-DPAT and > 30 min for alpha-Me 5-HT. 8-OH-DPAT induced depression of the reflex (IC50 0.85, 0.7-1.0 microM, geometric mean and 95% confidence limits) was blocked by spiperone (1 microM, apparent pA2 6.3) suggesting mediation via 5-HT1A receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7969810&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Comparison between venoconstrictor effects of sumatriptan and ergotamine in migraine patients.

Panconesi A, Anselmi B, Curradi C, Perfetto F, Piluso A, Franchi G.

Institute of Internal Medicine IV, University of Florence, Italy.

The vasoconstrictor activity of sumatriptan and ergotamine were compared by injecting these drugs in the hand vein of migraine subjects. We used the "venotest method", which permits the evaluation of the venoconstrictor effect of small doses of drugs, acting locally in the hand vein. Sumatriptan injected at increasing doses in the hand vein provoked contraction only at high doses (500 micrograms): venoconstriction lasted 5-15 minutes and was similar in intensity and duration to that induced by 0.5-1 micrograms of 5-hydroxytryptamine (5-HT). Likewise, ergotamine induced contraction only at a dose of 50 micrograms: this venoconstrictor effect was long lasting (at least 1 hour). Ergotamine-induced hand vein contraction, almost completely inhibited by ketanserin, seems mediated at least in part by 5-HT2 receptors, like the one induced by 5-HT and sumatriptan, already observed in a previous study. Clinical doses of ergotamine (0.25 mg intramuscular) and of sumatriptan (6 mg subcutaneous) do not provoke hand vein contraction for at least 1 hour: this could be due to a low activity of these drugs on the 5-HT2 vein receptors or a technique that is unsuitable to detect the vasoconstrictor effect of drugs given by the systemic route. The long lasting venoconstrictor effect of ergotamine may be due to a slow dissociation from receptor sites. The short vasoconstriction induced by sumatriptan could account for the recurrence of headache in many sumatriptan-treated migraine subjects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8014033&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
An open preference study with sumatriptan 50 mg and zolmitriptan 2.5 mg in 100 migraine patients.

Pascual J, Munoz R, Leira R.

Services of Neurology, University Hospital, Santander, Spain. pascualj unican.es

Understanding factors influencing patients' preference will improve guidance to make rational choices in expanded symptomatic migraine treatment. The objective of this open-label, cross-over study was to explore patients' preferences for sumatriptan 50 mg vs. zolmitriptan 2.5 mg tablets, focusing on factors influencing this preference. One hundred consecutive migraine patients attending our clinics were asked to treat three attacks with each medication and then fill out a preference questionnaire. Ninety-four migraineurs completed the trial and 42 (44%, 95% CI 34-58%) reported that they preferred zolmitriptan 2.5 mg over sumatriptan 50 mg tablets and 27 (29%, 20-38%) preferred sumatriptan 50 mg. The remaining 25 (27%, 18-36%) did not show any preference. For the initial treatment of the attacks, there were more patients needing just one tablet of zolmitriptan 2.5 mg compared with sumatriptan 50 mg (67 vs. 39%). The reasons for preference among those 69 patients who had shown preference for either of the two triptans were: a faster onset of action (speed of onset) (73%), a longer duration of the effects (39%), fewer adverse events (35%) and lower price (13%). Only one-quarter of the studied migraine population thought that sumatriptan 50 mg and zolmitriptan 2.5 mg were equivalent, which suggests that most migraine patients differentiate between triptans. A faster onset of action (speed of onset) was the most important reason for preference.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11531900&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
The effects of sumatriptan on pituitary secretion in man.

Franceschini R, Cataldi A, Garibaldi A, Cianciosi P, Scordamaglia A, Barreca T, Rolandi E.

Department of Internal Medicine, n. 6 University of Genoa, Italy.

Sumatriptan, a new antimigraine drug with high affinity and selectivity for certain 5-hydroxytryptamine (5-HT1D) receptor subtypes, was administered to 12 normal subjects, in order to investigate the effects of 5-HT receptor activation on anterior pituitary secretion. Sumatriptan increased plasma growth hormone (GH) levels from 2.5 +/- 0.5 mIU/l in basal conditions to 17.3 +/- 2.6 mIU/l 30 min after administration of the drug. After pre-treatment with cyproheptadine, an anti-serotoninergic drug known to inhibit GH secretion, the mean integrated sumatriptan-induced GH response decreased from 14.8 +/- 3.9 muI/l*hr to 3.7 +/- 1.7 mIU/l*hr. Sumatriptan administration did not have any effect on the secretion of the other anterior pituitary hormones. It is concluded that sumatriptan selectively increases GH secretion in man, but the exact nature of the receptors involved is not yet known.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8035909&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
5-Hydroxytryptamine1D-like receptors mediate contraction of partially depolarized rabbit renal arteries.

Choppin A, O'Connor SE.

Synthelabo Recherche, Department of Biology, Bagneux, France.

This study characterizes the 5-hydroxytryptamine (5-HT) receptors involved in the contraction of rabbit renal arteries which had been previously precontracted submaximally by partial depolarization. In the presence of ketanserin (10(-6) M) to block 5-HT2 receptors, 5-HT, 5-carboxamido-tryptamine (5-CT) and other 5-HT receptor agonists caused contraction of partially depolarized (22 mM KCl) rabbit renal arteries whereas they were without effect in quiescent tissues (4.7 mM KCl). 5-CT was the most potent agent tested, producing concentration-related increases in tension over the range of 10(-9) to 10(-6) M, attaining 44 +/- 2% of the tissue maximum with a EC50 of 4.8 +/- 0.9 x 10(-8) M. The relative order of agonist potency in partially depolarized tissues was 5-CT > 5-HT > 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H indole > or = sumatriptan > 8-hydroxy-2-(di-n-propyl-amino)tetralin > cisapride. Responses to 5-CT and sumatriptan were antagonized in a concentration-dependent fashion by methiothepin (3 x 10(-8)-3 x 10(-7) M). In the case of 5-CT, Schild analysis showed that this antagonism was competitive, giving a pA2 value of 7.72. Rauwolsine (3 x 10(-7)-10(-6) M) and metergoline (10(-6) M) also produced modest antagonism of 5-CT and sumatriptan-induced responses. With sumatriptan as agonist, rauwolscine gave a pKB of 6.43, however its antagonism of 5-CT appeared noncompetitive because it was associated with a reduction in maximum response (pKB' = 6.54).(ABSTRACT TRUNCATED AT 250 WORDS)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8071857&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Effects of sumatriptan on cerebral blood flow under normo- and hypercapnia in rats.

Fukuda M, Suzuki N, Maruyama S, Dobashi K, Kitamura A, Sakai F.

Department of Internal Medicine, School of Medicine, Kitasato University, Sagamihara, Japan. hukuta-m dd.catv.ne.jp

To investigate further the pharmacological mechanism of an anti-migraine drug, sumatriptan, a 5-HT1B/1D receptor agonist, we studied its effect on the cerebral circulation in seven anaesthetized rats, particularly during hypercapnia. After injection of 0.6 or 6.0 microg/kg sumatriptan succinate, no significant change in cerebral blood flow (CBF) was observed either in the striatum or in the parietal cortex. The increase in CBF both in the parietal cortex and the striatum during 5% CO2 inhalation was significantly less when sumatriptan succinate 6.0 microg/kg was injected. Sumatriptan appeared to have a vasoconstrictor effect on the relaxed vessels by CO2 inhalation. This mechanism might be attributable to vasoconstriction through activation of 5-HT1B receptors located in the vascular smooth muscle rather than 5-HT1B receptors in the vascular adventitia.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12133047&dopt=Abstract sumatriptan Imitrex