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PubMed1997

Simultaneous measurement of [3H]noradrenaline release and neurogenic contraction under identical conditions, to determine the prejunctional inhibitory effects of SKF 99101H and BRL 56905 in dog saphenous vein.

Using a tissue bath system which allowed the simultaneous measurement of electrically-induced [3H]noradrenaline release and neurogenic contraction under identical conditions, we investigated the prejunctional inhibitory activity of the selective 5-HT(1D/1B) receptor agonists BRL 56905 ((+/-)-3-amino-6-carboxamido-1,2,3,4-tetrahydrocarbazole) and SKF 99101H (3-(2-dimethylaminoethyl)-4-chloro-5-propoxyindole hemifumarate), compared to sumatriptan and 5-HT. Transmural electrical stimulation (2 Hz) of dog saphenous vein induced consistent increases in [3H]noradrenaline release as well as reproducible contractile responses (<10% decrease over four stimulation periods). BRL 56905, SKF 99101H, sumatriptan and 5-HT (60 nM-6 microM) inhibited electrically-evoked [3H]noradrenaline release and neurogenic contractile responses in dog saphenous vein. However, despite being measured under identical conditions, the inhibition of [3H]noradrenaline release was consistently greater than the inhibition of neurogenic contraction induced by a particular concentration of agonist, suggesting that neurogenic contractile responses in dog saphenous vein result from the combined release of noradrenaline and other non-noradrenergic neurotransmitters. Under the present assay conditions, since the agonists produced only small (BRL 56905, sumatriptan and 5-HT) or marginal (SKF 99101H) contractile responses, it is unlikely that this is the cause of the discrepancy observed between inhibition of release and inhibition of contraction. The inhibitory effects of BRL 56905, sumatriptan and 5-HT were blocked by the 5-HT(1D/1B) receptor antagonist methiothepin, consistent with the involvement of canine ca-5-HT(1D/1B) receptors in inhibiting neurotransmitter release and subsequent smooth muscle contraction in dog saphenous vein. The present results show that the novel 5-HT(1D/1B) receptor agonists BRL 56905 and SKF 99101H are at least as potent as sumatriptan and 5-HT, at activating prejunctional inhibitory ca-5-HT(1D/1B) heteroreceptors on sympathetic axon terminals in dog saphenous vein. In addition, when measured simultaneously in the same tissue preparation, [3H]noradrenaline release was inhibited to a much greater extent than neurogenic contraction by any particular agonist.

Animals↗
PubMed2003

Further characterization of the 5-HT1 receptors mediating cardiac sympatho-inhibition in pithed rats: pharmacological correlation with the 5-HT1B and 5-HT1D subtypes.

Serotonin (5-hydroxytryptamine; 5-HT) is capable of inhibiting the tachycardic responses elicited by sympathetic stimulation, but not by exogenous noradrenaline, in pithed rats pre-treated with desipramine. More recently, it has been shown that this cardiac sympatho-inhibitory response to 5-HT, mediated by prejunctional 5-HT1 receptors as well as putative 5-ht5A/5B receptors, is mimicked dose-dependently by the agonists CP 93,129 (r5-HT1B), sumatriptan (5-HT1B/1D) and PNU-142633 (5-HT1D). This study analysed further the pharmacological profile of the above 5-HT1 receptors. Continuous i.v. infusions of CP 93,129, sumatriptan or PNU-142633 (30 micro g kg(-1)min(-1) each) failed to modify the tachycardic responses to exogenous noradrenaline but inhibited those elicited by preganglionic (C7-T1) stimulation of the cardiac sympathetic outflow. These sympatho-inhibitory responses were unaltered after i.v. administration of physiological saline (1 ml kg(-1)) or the 5-HT1A receptor antagonist WAY 100635 (10 micro g kg(-1)). In contrast, the antagonist GR 127935 (5-HT1B/1D; 100 micro g kg(-1), i.v.) abolished the responses to CP 93,129, sumatriptan and PNU-142633, whilst SB224289 (5-HT1B; 300 micro g kg(-1), i.v.) abolished the responses to CP 93,129 without affecting those to sumatriptan and PNU-142633. Interestingly, BRL15572 (5-HT1D; 300 micro g kg(-1), i.v.) abolished the responses to PNU-142633 and attenuated those to sumatriptan, but not those to CP 93,129. WAY 100635, GR 127935, SB224289 and BRL15572, given alone at the above doses, failed to modify the sympathetically induced tachycardic responses. The 5-HT1 receptors producing cardiac sympatho-inhibition in pithed rats thus display the pharmacological profile of the 5-HT1B and 5-HT1D receptor subtypes.

Animals↗
PubMed2002

Non-invasive assessment of selective 5-HT(1B/1D)-receptor agonist-induced peripheral vascular effects in humans: comparison of different techniques.

OBJECTIVE: To compare the sensitivity of three non-invasive techniques for detecting serotonin (5-HT)(1B/1D)-receptor agonist-induced peripheral vascular effects in humans: the measurement of (1) systolic (SBP) and diastolic (DBP) blood pressures, (2) dorsal hand vein (DHV) diameter and (3) toe-arm systolic blood pressure gradient (DeltaSBP(toe-arm)). METHODS: A double-blind, placebo-controlled, three-way, cross-over study was performed in 12 healthy male volunteers. According to a randomly assigned allocation schedule, subjects were administered sumatriptan 3 mg, sumatriptan 6 mg or placebo subcutaneously. Measurements were performed at baseline, every 5 min for 30 min and at 40 min and 60 min after drug administration. SBP and DBP were recorded using a semi-automated oscillometric device. DHV diameter was measured using a linear variable differential transformer. DeltaSBP(toe-arm) was calculated after measuring toe and arm SBP with a strain-gauge technique. Sensitivity was evaluated with responsiveness statistics. RESULTS: Based on weighted mean and compared with placebo, sumatriptan 3 mg and 6 mg increased SBP by 3.3 mmHg ( P=0.023) and 6.4 mmHg ( P<0.001) and DBP by 5.0 mmHg ( P=0.006) and 7.5 mmHg ( P<0.001), respectively. Sumatriptan 3 mg and 6 mg decreased DHV diameter by 36% ( P=0.015) and 40% ( P=0.005), respectively. DeltaSBP(toe-arm) did not change. Peak changes were observed within 10-15 min after drug administration. The rank order of responsiveness was: BP > DHV diameter > DeltaSBP(toe-arm.) CONCLUSIONS: Clinically relevant doses of subcutaneous sumatriptan increased blood pressure and decreased DHV diameter without affecting DeltaSBP(toe-arm). The increase in blood pressure appeared to be dose dependent. Compared with DHV diameter and DeltaSBP(toe-arm), blood pressure measurement appeared to be the most sensitive technique for detecting selective 5-HT(1B/1D)-receptor agonist-induced peripheral vascular effects in humans.

Adult↗
PubMed2004

Cluster headache: symptomatic treatment.

The clinical management of cluster headache (CH) attacks requires a symptomatic treatment that is rapidly effective in resolving or significantly reducing symptoms. First-choice drugs for the symptomatic treatment of CH are subcutaneous sumatriptan at a dose of 6 mg and 100% oxygen inhalation at a rate of 7 l/min for no more than 15 min. Sumatriptan acts by suppressing pain and the accompanying autonomic phenomena, with no substantial differences in its mechanism of action between episodic and chronic CH. The drug can be used for prolonged periods without loss of efficacy or safety and its side-effects are generally mild or moderate. Oxygen inhalation has a number of advantages over drug therapy: it is free from side-effects, has no contraindications--unlike sumatriptan, it can be used in patients with cardiac, cerebral or peripheral vascular disease and with kidney, liver or lung disease--acts rapidly and can be administered several times a day. Its disadvantages are that it is scarcely practical and may induce a "rebound effect". Sumatriptan nasal spray, zolmitriptan and dihydroergotamine nasal spray are scarcely effective. After the introduction of sumatriptan, ergotamine tartrate has been relegated to a secondary role in the symptomatic treatment of CH. Among other non-drug and topical drug treatment options, hyperbaric oxygen therapy and the intranasal application of 10% cocaine hydrochloride and 10% lidocaine in the sphenopalatine fossa have also proved effective.

Clinical Trials as Topic↗
PubMed1996

Effect of antimigraine drugs on dural blood flows and resistances and the responses to trigeminal stimulation.

The effects of 2 antimigraine drugs sumatriptan and dihydroergotamine on dilatation of the middle meningeal artery elicited by stimulation of the trigeminal ganglion at the entry point of the first and second divisions was investigated in cats. Carotid and middle meningeal arterial blood flows and resistances were measured in 9 cats anesthetised with chloralose. Electrical stimulation of either trigeminal ganglion produced a frequency-dependent decrease in resistance of the carotid artery ipsilaterally and the middle meningeal artery bilaterally. The intravenous injection of sumatriptan increased carotid and meningeal vascular resistance, but this response was not prolonged. The intravenous injection of dihydroergotamine produced a larger and more prolonged vasoconstriction in these 2 beds than did sumatriptan. Dihydroergotamine, but not sumatriptan, blocked some components of the vascular response induced by stimulation of the trigeminal ganglion. Dihydroergotamine and sumatriptan have a different spectrum of activity on cranial circulatory beds and neither of them is able to reduce trigeminal-induced vasodilatation by blocking antidromic activation of trigeminal nerve fibres in cats at the doses used in these experiments.

Animals↗
PubMed2005

Anti-migraine action of triptans is preceded by transient aggravation of headache caused by activation of meningeal nociceptors.

Consistent with previous accounts, some of the patients visiting our pain clinic during the course of a migraine attack have indicated-without solicitation-that sumatriptan injection initially intensified their headache before they were able to appreciate any pain relief. In this study, those patients who came forward complaining about pain exacerbation were asked to rate their headache intensity every 5 min. Within 5-15 min of sumatriptan injection, 17 of the 31 patients studied (55%) reported that their migraine pain intensified for 10-15 min before they started to notice any pain relief. Similar pattern of pain exacerbation was also observed in migraine attacks treated with oral formulation of almotriptan, eletriptan, rizatriptan, and zolmitriptan. To investigate the possible mechanism underlying this transient exacerbation of pain, we examined whether intravenous administration of sumatriptan can alter the response properties of C- and Adelta-meningeal nociceptors in the rat. Five to twenty minutes after intravenous administration of 300 microg/kg sumatriptan, 8/10 C-units and 2/8 Adelta-units increased their firing rate, and 6/10 C-units and 7/8 Adelta-units developed mechanical hyper-responsiveness to dural indentation. The minimal effective dose for activation and sensitization of meningeal nociceptors by sumatriptan was 3 microg/kg, suggesting that relatively low levels of triptans entering the circulation shortly after their administration can alter the physiological properties of meningeal nociceptors and produce a transient exacerbation of headache.

Action Potentials↗
PubMed1992

5-Hydroxytryptamine receptor agonists for the abortive treatment of vascular headaches block mast cell, endothelial and platelet activation within the rat dura mater after trigeminal stimulation.

Antidromic stimulation of small caliber trigeminal axons causes neurogenic inflammation in the dura mater and tongue as evidenced by marked increases in mast cell activation, protein extravasation, as well as in the numbers of endothelial cytoplasmic vesicles, endothelial microvilli and platelet aggregates within ipsilateral post-capillary venules. In this report, we examined the effects of pretreatment with serotonin1 receptor agonists, dihydroergotamine (50 micrograms/kg, i.v.) and sumatriptan (100 micrograms/kg, i.v.) on the light and electron microscopic changes which develop after trigeminal ganglion stimulation. Both dihydroergotamine and sumatriptan are useful in the acute treatment of vascular headaches and bind with high affinity to 5-HT1D receptors. Both drugs decreased significantly the number of dural vessels showing endothelial or platelet changes and the numbers of activated mast cells, but did not affect the neurogenic response in the tongue. The drugs also blocked the accumulation of horseradish peroxidase reaction product within the endothelium and perivascular space on the stimulated side. The receptor is not present on trigeminovascular fibers innervating extracranial cephalic tissues. Drug mechanism probably involves inhibition of a proximal step in the pathophysiological cascade (e.g., via activation of a prejunctional receptor) because (a) receptors for sumatriptan have not been identified on mast cells whereas the inflammatory response was attenuated in mast cells as well as within platelets and the endothelium and (b) previous work indicates that sumatriptan and dihydroergotamine block neurotransmitter release. Hence, constriction of vascular smooth muscle mediated by postjunctional 5-hydroxytryptamine receptors is unlikely to explain the anti-inflammatory actions of dihydroergotamine or sumatriptan reported here.

Animals↗
PubMed1998

5-HT1B receptor binding in degenerative movement disorders.

Using [3H]sumatriptan as a radioligand, 5-hydroxytryptamine (5-HT)1B receptors were examined in posterior striatum and midbrain post-mortem tissue sections of 12 patients who had died from representative degenerative movement disorders as compared to nine controls. In the control human basal ganglia, the highest densities of [3H]sumatriptan binding were observed in the globus pallidus and substantia nigra. No significant change in the density of [3H]sumatriptan binding sites was found in the striatum and substantia nigra of the six Parkinson's disease brains. In the two brains from patients with progressive supranuclear palsy an increase was found in the densities of [3H]sumatriptan binding sites, most marked in the substantia nigra. In contrast, [3H]sumatriptan labelling was almost absent in the striatonigral degeneration brain and was markedly reduced in the three Huntington's disease brains. This study indicates that the status of 5-HT1B receptors is different in each degenerative movement disorder and suggests that human 5-HT1B receptors are located somatodendritically on GABAergic and peptidergic caudate-putamen neurons which project to the substantia nigra and globus pallidus, where these receptors are presynaptic.

Aged↗
PubMed1997

The selectivity of MDL 74,721 in models of neurogenic versus vascular components of migraine.

MDL 74,721 (R)-2-(N1,N1-dipropylamino)-8-methylaminosulfonylmethyl-1,2,3,4-te trahydronaphthalene, a sulfonamidotetralin, has been found to exhibit a 10,000-fold greater potency in neurogenic versus vascular models of migraine. Sumatriptan, a relatively pure 5-HT1D/5-HT1B receptor agonist, also showed higher potency versus neurogenic inflammation. However, for sumatriptan the potency difference (100-fold) in the two pathophysiological models was less pronounced than seen for MDL 74,721. The affinity profile of MDL 74,721 at 5-HT1 receptor subtypes may in part explain its ability to differentiate these two physiological responses. MDL 74,721 demonstrated nanomolar affinity for 5-HT1A (12.7 +/- 0.3 nM) and 5-HT1D (41.3 +/- 10.9 nM) but considerably lower affinity for 5-HT1B receptors (> 1000 nM). Serotonin-like activity was seen in in vitro functional assays including inhibition of forskolin-stimulated cAMP accumulation in human 5-HT1D receptor-transfected fibroblasts or eliciting vasoconstriction in isolated human pial arteries. The intrinsic activity (relative to 5 - HT[E(Amax)]) and affinity (pD2) for the human cerebrovascular 5-HT receptors were: 5-HT (100%, 7.51 +/- 0.09), sumatriptan (94%, 6.85 +/- 0.1) and MDL 74,721 (66%, 5.70 +/- 0.23). In anaesthetised cats, treatment with MDL 74,721 resulted in a dose-related reduction in the percentage of carotid flow going through the arteriovenous anastomoses to the lungs, with an ED50 of 0.3 mg/kg i.v., the same as sumatriptan. However, in the guinea-pig neurogenic model, MDL 74,721 inhibited plasma protein extravasation with an ED50 of 0.023 microg/kg compared to 2.5 microg/kg for sumatriptan. MDL 74,721 was also effective in this model (in rats) after oral administration. In conclusion, MDL 74,721 demonstrates a preclinical profile consistent with anti-migraine efficacy. Its marked preference for inhibiting neurogenic inflammation makes this compound a useful tool for assessing the relative contribution of this pathophysiological mechanism to the human disease state.

Animals↗
PubMed1995

Influence of a selective 5HT1-receptor agonist GR43175 on platelet responsiveness.

The possible interaction of sumatriptan, a selective 5HT1-receptor agonist, with platelet responsiveness has been investigated. Stimulation of platelet rich plasma with sumatriptan (1-100 microM) did not induce shape change, aggregation or modification of intraplatelet cytosolic calcium levels. Total inhibition of aggregation induced by 20 microM 5HT was observed in platelets preincubated for 20 min with 100 microM sumatriptan. In the same model, platelet stimulation with 4 microM adenosine 5'-diphosphate (ADP), concentration known to induce an irreversible single-phase curve, determined a decrease of aggregatory response. Concentrations from 1 microM to 50 microM of sumatriptan did not influence the aggregatory response induced by 5HT and ADP. These effects appear not to be determined by modifications of platelet calcium homeostasis. The possibility to modulate platelet responsiveness by sumatriptan offers a further approach for evaluating the probable link between platelet behaviour and pathophysiology of migraine.

Adenosine Diphosphate↗
PubMed1999

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

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.

Adolescent↗
PubMed2002

Almotriptan is an effective and well-tolerated treatment for migraine pain: results of a randomized, double-blind, placebo-controlled clinical trial.

Almotriptan is a novel and specific serotonin 5-HT1B/1D agonist for the acute treatment of migraine. This randomized, single-dose, double-blind, multicentre, study assessed the efficacy and safety of oral almotriptan (12.5 mg and 25 mg) in patients with migraine, and compared it with the standard treatment (sumatriptan 100 mg) and placebo. A total of 668 patients treated one migraine attack of moderate or severe intensity with study medication. The primary efficacy assessment was migraine pain relief, improvement from severe or moderate pain to mild or no pain, at 2 h after treatment. Response rates, stratified for variation in baseline pain levels, for both almotriptan doses were equivalent to sumatriptan and significantly better than placebo. Other efficacy assessments confirmed the equivalence of the almotriptan groups with the sumatriptan group. Almotriptan 12.5 mg was as well tolerated as placebo (P=0.493) and significantly better tolerated than sumatriptan (P<0.001), in terms of the overall incidence of adverse events. There was no statistically significant difference in the incidence of adverse events between almotriptan 25 mg and sumatriptan 100 mg (P=0.376). The results from this large clinical study indicate that the new, specific 5-HT1B/1D agonist, almotriptan, is an effective and well-tolerated treatment for migraine pain.

Administration, Oral↗
PubMed2002

Preclinical studies characterizing the anti-migraine and cardiovascular effects of the selective 5-HT1D receptor agonist PNU-142633.

The present study describes the preclinical pharmacology of a highly selective 5-HT1D receptor agonist PNU-142633. PNU-142633 binds with a Ki of 6 nm at the human 5-HT1D receptor and a Ki of> 18 000 nm at the human 5-HT1B receptor. The intrinsic activity of PNU-142633 at the human 5-HT1D receptor was determined to be 70% that of 5-HT in a cytosensor cell-based assay compared with 84% for that of sumatriptan. PNU-142633 was equally effective as sumatriptan and a half-log more potent than sumatriptan in preventing plasma protein extravasation induced by electrical stimulation of the trigeminal ganglion. Like sumatriptan, PNU-142633 reduced the increase in cat nucleus trigeminal caudalis blood flow elicited by electrical stimulation of the trigeminal ganglion compared with the vehicle control. The direct vasoconstrictor potential of PNU-142633 was evaluated in vascular beds. Sumatriptan increased vascular resistance in carotid, meningeal and coronary arteries while PNU-142633 failed to alter resistance in these vascular beds. These data are discussed in relation to the clinical findings of PNU-142633 in a phase II acute migraine study.

Analgesics↗
PubMed1996

Prescribing practices for the management of headache in Newfoundland and Labrador.

To assess the impact of sumatriptan in clinical practice, we undertook a retrospective analysis of the government of Newfoundland and Labrador's prescription drug program data base for 35 consecutive patients prescribed sumatriptan. The number of doses of all drugs prescribed ranged from 121 to 18,874 on from 4 to 357 prescriptions per patient over 1 to 19 months. The mean number of doses of analgesic drugs prescribed before sumatriptan therapy was 56 per month and after initiation of sumatriptan was 46 per month. The prescribing of multiple analgesics was common; 79% received three or more different analgesics. Twenty-two (63%) patients were prescribed medications indicated for the prophylaxis of migraine concomitantly with drugs indicated for symptomatic treatment. Twenty-four (69%) patients were prescribed medication capable of inducing migraine. We conclude that sumatriptan did not have a major impact on the outcomes of these patients judged by their use of analgesics. The simplest explanation is that many of the patients were suffering from analgesic-induced headache rather than migraine. In addition, we conclude that there were deficiencies in prescribing practices including numbers, quantities, and choice of analgesics; the use of analgesics concomitantly with drugs indicated for migraine prophylaxis; and the use of drugs capable of inducing migraine. Further research is required to validate these findings.

Analgesics↗
PubMed2001

Reduction in the intensity of abortive migraine drug use during coumarin therapy.

OBJECTIVE: To investigate the impact of coumarin therapy on migraine attack frequency. BACKGROUND: Sporadic case reports and clinical studies have described beneficial effects of coumarin therapy on migraine severity. DESIGN AND METHODS: A retrospective follow-up study based on a prescription database covering a population of 450 000 was conducted. All patients using an abortive migraine drug (ergotamine or sumatriptan) and subsequently treated with either coumarin (index group) or low-dose acetylsalicylic acid (control group) were analyzed. The impact of coumarin and low-dose acetylsalicylic acid on the frequency of migraine attacks was assessed by measuring the intensity of ergotamine and sumatriptan use, in defined daily doses per month per patient, before and during coumarin or acetylsalicylic acid treatment. In addition, a "therapeutic intensity reduction" was determined for each patient. RESULTS: The study population consisted of 92 patients; 35% had been prescribed coumarin and 65% had been prescribed low-dose acetylsalicylic acid after the initiation of ergotamine or sumatriptan. Two thirds of the study population was treated with ergotamine. Overall, ergotamine and sumatriptan use for the coumarin cohort decreased from 6.4 defined daily doses per month prior to coumarin treatment to 3.0 defined daily doses during coumarin treatment, compared with a reduction from 5.2 defined daily doses per month to 4.4 defined daily doses per month for the low-dose acetylsalicylic acid cohort (P>.05). The therapeutic intensity of ergotamine and sumatriptan use was significantly decreased by 40% for the coumarin cohort, compared with 4.7% for the low-dose acetylsalicylic acid cohort (P=.004). CONCLUSIONS: We observed that coumarin treatment was clearly associated with a reduction in the therapeutic intensity of abortive migraine drug use in comparison with low-dose aspirin treatment. This suggests that, overall, the coumarin cohort had experienced a substantial reduction in the frequency of migraine attacks during anticoagulation treatment. Our findings, as well as those of others, justify a controlled clinical trial to further establish the effects of coumarin therapy on migraine severity and its possible role in the prophylactic management of patients suffering from migraine.

Anticoagulants↗
PubMed2002

Comparison of triptan tablet consumption per attack: a prospective study of migraineurs in Spain.

OBJECTIVES: To compare patient self-reported tablet consumption of rizatriptan 10 mg per attack (24 hours) with that of sumatriptan 50 mg, zolmitriptan 2.5 mg, and naratriptan 2.5 mg on an unselected, prescription-based, Spanish migraine population. METHODS: One hundred twenty community pharmacies recruited patients with migraine, who used their pharmacies, to fill a triptan prescription. In diaries, patients recorded baseline pain intensity and the number of triptan tablets and additional medication taken per attack. Patients treated a maximum of three attacks. Analysis of variance or the Student t test and chi-square or Fisher exact tests were used for univariate comparisons. Hochberg corrections were used for multiple-group comparisons. A generalized estimating equation method was used to correct for within-subject correlation. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Two hundred thirty-one patients (84% women) treated 589 evaluable migraine attacks (sumatriptan, n = 135; naratriptan, n = 90; zolmitriptan, n = 149; rizatriptan, n = 149). Triptan tablet consumption per attack (mean +/- SD) for rizatriptan (1.24 +/- 0.56) was significantly lower than that of sumatriptan (1.75 +/- 1.2; P< .05), zolmitriptan (1.61 +/- 0.86; P < .05), or naratriptan (1.46 +/- 0.62; P= .05). The average number of triptan tablets taken and additional medication use increased according to baseline pain severity. More attacks were treated with one tablet of rizatriptan (81.2%) than with one tablet of sumatriptan (51.9%), zolmitriptan (55.7%), or naratriptan (60%). The probability of using more than one triptan tablet per attack (24 hours) was more than three times greater for sumatriptan (adjusted OR = 3.71; CI, 2.05 to 6.7; P = .001) and zolmitriptan (adjusted OR = 3.32; CI, 1.82 to 6.17; P = .001), and more than two times greater for naratriptan (adjusted OR = 2.66; CI, 1.36 to 5.21; P =.004) than for rizatriptan. CONCLUSIONS: Rizatriptan was associated with significantly lower triptan tablet use and additional medication use per attack than the other triptans. Additional randomized studies are needed to confirm the conclusions of this study.

Female↗
PubMed1998

Effects of the novel high-affinity 5-HT(1B/1D)-receptor ligand frovatriptan in human isolated basilar and coronary arteries.

The contractile actions of the novel high-affinity 5-hydroxytryptamine (5-HT(1B/1D)) ligand, frovatriptan (formerly VML 251/SB-209509) were investigated in human isolated basilar and coronary arteries in which the endothelium had been removed. Basilar arteries were obtained post mortem, and coronary arteries were obtained from patients undergoing heart transplant (recipient) or from donor hearts that were not suitable for transplant. Frovatriptan was a potent contractile agent in isolated basilar artery with a -log mean effective concentration (EC50) value of 7.86 +/- 0.07 and intrinsic activity of 1.25 +/- 0.10 relative to 5-HT (n = 4). Frovatriptan was 8.5-fold more potent than sumatriptan, which produced a -log EC50 value of 6.93 +/- 0.09 and intrinsic activity 11.1 +/- 0.08 relative to 5-HT (n = 4). In coronary arteries, frovatriptan produced contraction with -log EC50 values of 7.38 +/- 0.12 and 7.81 +/- 0.2 in recipient (n = 7) and donor (n = 3) arteries, respectively. The relative degree of contraction of frovatriptan was lower than that of 5-HT, with relative intrinsic activities of 0.42 +/- 0.06 and 0.40 +/- 0.09, respectively. Sumatriptan produced contraction of human recipient and donor arteries with -log EC50 values (intrinsic activity) of 6.57 +/- 0.13 (0.79 +/- 0.27; n = 6) and 7.35 (1.41; n = 2), respectively. Furthermore, marked bell-shaped responses were apparent for frovatriptan in coronary arteries, with relaxation occurring at concentrations >6 microM in some tissues. In contrast, no bell-shaped concentration-response curves were apparent for sumatriptan or 5-HT. Threshold concentrations for frovatriptan-induced contractions were also different between basilar (>2 nM) and coronary arteries (>20 nM). No separation of threshold activity was observed with sumatriptan or 5-HT. These data show that frovatriptan produces constriction of human isolated basilar and coronary arteries. However, frovatriptan produces a complex pharmacologic response in the coronary artery, with threshold contractile activity requiring approximately 10-fold greater concentrations of agonist than in the basilar artery. Frovatriptan also shows a differential pharmacologic profile compared with sumatriptan in coronary arteries, with reversal of tone predominating at high concentration.

Basilar Artery↗
PubMed1995

Acute treatment of migraine attacks.

Migraine is a chronic neurological disorder, characterized by attacks of severe, usually unilateral and throbbing headache accompanied by nausea, vomiting, and photophobia and photophobia. Sometimes transient neurological (aura) symptoms may precede or accompany the headaches. Acute drug therapy comprises nonspecific drugs, including simple analgesics and non-steroidal anti-inflammatory drugs, often in combination with antiemetics, and specific antimigraine drugs, such as ergotamine, dihydroergotamine and sumatriptan. Sumatriptan is a potent and selective serotonin1D receptor agonist, which can be administered orally and via the subcutaneous or intranasal route. The drug is well tolerated and is consistently highly effective in most patients. Significant limitations, however, include the occurrence of chest symptoms, suggestive of cardiac ischaemia; recurrence of the headache within 24 h after initial successful treatment; and in a minority of patients, abuse of sumatriptan with daily 'sumatriptan-dependent headaches'. Administration during the aura phase does not affect the aura itself, but is not recommended because the subsequent headache will not be prevented in that case. Preliminary data of new serotonin1D receptor agonists, such as 311C90 and MK-462 are promising in terms of increased efficacy after oral administration, but side-effect profile and incidence of headache recurrence are similar to those observed after the use of sumatriptan. Intranasal administration of dihydroergotamine may also be effective, but data are very limited.

Adolescent↗