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PubMed1998

Successful treatment of headache related to intravenous immunoglobulin with antimigraine medications.

In order to investigate headache related to intravenous immunoglobulin, we studied a 36-year-old woman with a history of migraine receiving weekly intravenous immunoglobulin for refractory myasthenia gravis who experienced severe headaches with each treatment. Neurological examination, CT scan of the head, and a lumber puncture after the first headache were normal. Significant therapeutic response was based upon 50% reduction in pain and associated features. Headache features included throbbing pain which worsened with head movement and was associated with severe photophobia and nausea. Sumatriptan, 6 mg subcutaneous, reduced headache significantly with resolution of associated complaints. Treatment prior to intravenous immunoglobulin with dihydroergotamine mesylate resulted in development of only a mild dull ache without further development of severe head pain. Dihydroergotamine mesylate was also abortive in the few instances when the headache worsened. Headaches associated with intravenous immunoglobulin may have features of migraine and may be successfully prevented and/or treated with 5-HT1D receptor agonists.

Adult↗
PubMed2001

Immunological aspects in migraine: increase of IL-10 plasma levels during attack.

In the present study, 23 patients with migraine without aura were monitored during a migraine attack. Plasma levels of interleukin (IL)-4, IL-5, IL-10, and interferon-gamma were measured by enzyme-linked immunosorbent assay techniques. Interestingly, we observed low to undetectable IL-5 and IL-4 levels, whereas high IL-10 levels were seen in 52.2% of the patients. Interferon-gamma plasma levels were undetectable in all patients. After treatment with sumatriptan, 10 patients showed a subsequent decrease in IL-10 and an increase in both IL-4 and IL-5 plasma levels. Although these findings are derived from a limited number of patients, the apparent return to the IL-4 and IL-5 cytokine profile observed during the interictal period leads us to speculate that a preferential enhancement of TH2-type cytokine production may contribute to the pathogenesis of migraine.

Adult↗
PubMed2002

Cryptic pituitary hemorrhage presenting with headache.

We report a case of pituitary hemorrhage and review the literature on that condition. Our patient presented with a sudden bifrontal headache associated with vague transient visual blurring but without nausea or other associated symptoms. After a negative workup at another hospital, including an unremarkable brain computed tomography without contrast, and resolution of headache following treatment with injectable sumatriptan, he was diagnosed with "atypical migraine." The patient's symptoms soon returned, and brain magnetic resonance imaging revealed an enlarged, cystic pituitary gland with a small intraparenchymal hemorrhage.

Adenoma↗
PubMed2002

Clinical benefits of early triptan therapy for migraine.

Although triptans have been proven effective for acute treatment of migraine, reserving them for moderate or severe pain may produce suboptimal pain relief and higher rates of recurrence. Recent evidence indicates that early intervention at the onset of pain improves outcomes. Post hoc analysis of a long-term, open-label European study of almotriptan 12.5 mg found that the percentage of attacks rendered pain-free at 2 hours was significantly greater when patients treated mild pain (84%) than when the intervention occurred during moderate or severe pain (53%). A similar pattern emerged with respect to the consistency of pain relief, with a significant advantage for early intervention (88% versus 56%, respectively). A difference in favor of early intervention was also seen with respect to recurrence, need for rescue medication, and adverse events. The recurrence rate was significantly lower in patients treating mild pain (28%) than in those delaying treatment until the pain became moderate or severe (33%), which suggests that achieving pain freedom results in less recurrence. These results were generally replicated in post hoc analysis of a subgroup of patients from a randomized, placebo-controlled trial (the Spectrum Study) of oral sumatriptan 50 mg in migraineurs. This analysis demonstrated that with early intervention, pain was less likely to intensify, fewer attacks required redosing, more attacks remained pain-free 24 hours postdose, and normal function returned more quickly. In sum, early intervention with triptans can improve outcomes, avoiding much of the pain and disability associated with treating moderate or severe attacks.

Acute Disease↗
PubMed2002

Pharmacology of the selective 5-HT(1B/1D) agonist frovatriptan.

OBJECTIVE: To determine the pharmacological profile of frovatriptan. BACKGROUND: Frovatriptan is a new 5-HT(1B/1D) agonist developed for the treatment of migraine. METHODS: Pharmacological studies were performed using in vitro and in vivo techniques. RESULTS: Radioligand-binding studies showed that frovatriptan has a high affinity for 5-HT(1B) and 5-HT(1D) receptors, and moderate affinity for 5-HT(1A), 5-HT(1F), and 5-HT(7) receptors. In vitro, frovatriptan acts as a potent full agonist at human cloned 5-HT(1B) and 5-HT(1D) receptors, and as a moderately potent full agonist at 5-HT(7) receptors. Studies of frovatriptan in isolated human arteries demonstrated a lower threshold for constriction of cerebral than coronary vasculature and a bell-shaped dose-response curve was apparent in the coronary arteries. In anesthetized dogs, frovatriptan administration produced no measurable effect on cardiac function or on blood pressure. Frovatriptan had no effects on coronary blood flow following transient coronary artery occlusion, whereas sumatriptan produced a prolonged and significant decrease in coronary blood flow. CONCLUSION: The pharmacology of frovatriptan suggests that it should be an effective agent for the acute treatment of migraine, with a low potential for undesirable peripheral effects.

Animals↗
PubMedDate not supplied

[Pharmacotherapy: migraine and depression. Therapy with sumatripten and citalopram: perioperative anaesthesiological risk assessment].

We report on a case of a patient with migraine and depression treated with citalopram and sumatriptan. The drug evaluation is presented using the actual summaries of product characteristics (SPC, "Fachinformationen"). Particular the individual perioperative anaesthesiological risk assessment regarding the pharmacodynamic and pharmacointeractions is discussed.

Anesthetics↗
PubMed1993

Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase.

An intronless gene encoding an additional human serotonin (5-HT) 5-HT1-like receptor subtype was isolated from a human genomic library with probes obtained from degenerate PCR primers used to amplify 5-HT-receptor-specific sequences. The highest degree of homology was found with the 5-HT1E subtype (70%) and the 5-HT1D alpha (63%) and 5-HT1D beta (60%) receptors. RNA for this gene was detected in the human brain but was not detected in kidney, liver, spleen, heart, pancreas, and testes. High-affinity (Kd = 9.2 nM) 3H-labeled 5-HT binding was detected. Competition studies revealed the following rank order of potencies for serotonergic ligands: 5-HT > sumatriptan >> 5-carboxyamidotryptamine > 8-hydroxy-2(di-1-propylamino)tetralin > spiperone. 5-HT produced a dose-dependent inhibition of forskolin-stimulated cAMP accumulation (EC50 = 7.9 nM) in transfected cells. These properties distinguish this receptor from any previously characterized and establish a fifth 5-HT1-like receptor subtype (5-HT1F) coupled to the inhibition of adenylate cyclase.

Adenylyl Cyclase Inhibitors↗
PubMed2000

Vestibular schwannoma surgery and headache.

The aim of the study was to evaluate aetiological factors for postoperative headache after vestibular schwannoma (VS) surgery with respect to asymmetric activation of vestibular reflexes. After surgery, 27 VS patients with persistent postoperative headache, 16 VS patients without headache and 9 healthy controls were examined. The vestibular, cervicocollic and cervicospinal reflexes were evaluated to study whether asymmetric activation of vestibular reflexes could cause headache. The effect of neck muscle and occipital nerve anaesthesia and the effect of sumatriptan on headache were also evaluated. The vestibular function of VS patients with headache did not differ from that of VS patients without headache, but was abnormal when compared to that of normal controls. The cervicospinal and cervicocollic reflexes did not differ in the patient groups. Injection of lidocaine around the operation scar gave pain relief to two patients, and one of them had occipital nerve entrapment. Infiltration of lidocaine deep in the neck muscles in the vicinity of the C2 root did not alleviate headache, but caused vertigo. Nine patients with musculogenic headache got pain relief from supportive neck collars, and two patients with cervicobrachial syndrome got pain relief from manual neck traction. The study shows that asymmetric activation of cervicocollic reflexes does not seem to be the reason for headache. Headache seems to be linked to neuropathic pain, allegedly caused by trigeminal irritation of the inner ear and the posterior fossa, which has recently been linked to vascular pain.

Adult↗
PubMed1997

Common noncompartmental pharmacokinetic variables: are they normally or log-normally distributed?

We investigated the hypothesis that distributions of continuous pharmacokinetic variables are positively skewed in nature and that logarithmic transformation of these variables restores normality. The distributions of common continuous noncompartmental pharmacokinetic variables were investigated for four different Glaxo Wellcome compounds, administered by three different routes of administration: ranitidine (po), sumatriptan (sc), ondansetron (iv), and bismuth, from ranitidine bismuth citrate (po). The distributions of all the investigated noncompartmental pharmacokinetic variables were adequately described by a log-normal distribution, whereas statistically significant departures from normality occurred in the majority of cases. Thus, unless there is strong and consistent evidence for a departure from log-normality, the parametric statistical analysis of common noncompartmental pharmacokinetic variables should be carried out after a priori log transformation.

Bismuth↗
PubMed1998

Retinal plasma extravasation in animals but not in humans: implications for the pathophysiology of migraine.

High-intensity electrical stimulation of the trigeminal ganglion is accompanied by mast cell degranulation, vasodilatation, increased endothelial permeability and leakage of albumin from postcapillary venules within the dura mater. Overall, the histological appearance suggests an evolving sterile inflammatory response. This neurogenic inflammation within the meninges has been suggested as a model to explain the pain in migraine and cluster headache, and has been used to characterize the pharmacology of anti-migraine compounds. Using the rat model of neurogenic inflammation, the albumin extravasation ratio (stimulated : unstimulated side) in vehicle-treated animals in the dura and retina was 1.60 +/- 0.11 and 1.76 +/- 0.18, respectively (n = 10; values are mean +/- SEM). Pretreatment with sumatriptan (n = 9) produced a highly significant reduction in the ratio of extravasation within the dura to 1.10 +/- 0.06 (P = 0.002) and in the retina to 0.96 +/- 0.06 (P = 0.001), as did the neurokinin-1 receptor antagonist RP 67580 (n = 12) in the dura (1.04 +/- 0.11, P = 0.002) and retina (1.08 +/- 0.06, P = 0.001). These data demonstrate increased endothelial permeability and leakage of albumin not only in the dura but also in the retina. In a second stage we investigated possible extravasation in the human retina in acute migraine (n = 8) and cluster headache (n = 5) using fluorescein or indocyanine angiography. No increased endothelial permeability or leakage of dye could be found in the human retinal or choroidal vessels during headache attacks or in the headache-free interval in persons suffering from both migraine and cluster headache. These data raise the possibility that neurogenic inflammation is not a major factor in headache attacks in migraine or cluster headache.

Adult↗
PubMedDate not supplied

Triptan use preceding life-threatening arrhythmias in charcot-marie-tooth: a case report and review of the literature.

Charcot-Marie-Tooth (CMT) identifies a rare group of inherited disorders of the peripheral nervous system that share clinical features of sensory and motor defects, but rarely affect cardiac function. The few references that relate CMT to cardiac pathology of any sort are so rare that their finding was considered either fortuitous or suggestive of an erroneous diagnosis. The 5-HT1B/1D agonists or triptan drug class was introduced to the clinical practice arena in the early 1990s, and since then several cardiac adverse events have been associated with its use. The authors report the case of a 41-year-old white woman with CMT who had been recently prescribed sumatriptan and who presented with sudden loss of consciousness associated with ventricular fibrillation. These findings have been reported in the literature, but the association of triptan-induced arrhythmias and degenerative neuropathies remains to be established. The authors propose, through this case report and review, that the relative rarity of CMT coupled with the lack of further investigation of their association with conduction abnormalities might have set the stage for underestimation of the potentially synergistic effect with triptans in their capacity to generate life-threatening arrhythmias.

Adult↗
PubMed1996

5-HT1-like receptor-mediated contraction in the human internal mammary artery.

We wished to characterize the 5-hydroxytryptamine (5-HT) receptors mediating vasoconstriction in the human internal mammary artery (IMA). Segments of the IMA obtained from patients undergoing coronary by-pass surgery were suspended in an organ bath and exposed to 5-HT and sumatriptan (SUM), a 5-HT1-like receptor agonist, in the presence and absence of potassium chloride (KCl) and angiotensin II. 5-HT induced concentration-dependent contractions in all quiescent and pre-contracted preparations. SUM induced small contractions in 70% of quiescent IMA rings, whereas it elicited marked and concentration-dependent contractions in all of the preparations given a moderate tone by a threshold concentration of KCl and angiotensin II. The efficacy of SUM was higher in precontracted arteries. Concentration-effect curves (CEC) of 5-HT and SUM were not affected by the 5-HT3-receptor antagonist tropisetron (1 microM). The nonselective antagonist, methiothepin (30 nM), shifted the CEC of SUM to the right. 5-HT2A-receptor antagonist, ketanserin (1 microM) inhibited responses to 5-HT, whereas it affected only the responses to the smaller concentrations of SUM. When methiothepin (30 nM) was applied in the presence of ketanserin (1 microM), a further inhibition in the responses to 5-HT was observed. These results suggest that 5-HT1-like receptors mediate the contractile action of SUM and contribute to that of 5-HT in IMA.

Adult↗
PubMed2000

Phenylephrine precontraction increases the sensitivity of rabbit femoral artery to serotonin by enabling 5-HT1-like receptors.

We used selective receptor antagonists to identify the receptors mediating the isometric contractile response to serotonin in control and phenylephrine (PHE)-precontracted rabbit femoral artery rings. Serotonin, in the absence of PHE, elicited monophasic concentration-response curves (CRCs) early, but biphasic CRCs late in the course of the study. In the monophasic curves, the threshold and maximal concentrations were 10 and 1,000 microM, respectively. In biphasic CRCs, the threshold and maximal concentrations of the first phase were 0.03 and 3 microM, respectively. The respective values for the second phase were 10 and 1,000 microM. Prazosin, 0.1 microM, a selective alpha1-adrenoceptor antagonist, inhibited the monophasic curves, but only the second phase of the biphasic curves. Ritanserin, 0.01 microM, a selective 5-HT2A-receptor antagonist, shifted the first phase of the biphasic serotonin CRCs to the right but had little effect on the second phase. PHE increased the sensitivity of rabbit femoral artery response to serotonin. This amplified response to serotonin was antagonized by 0.01 microM GR 127935T, a selective 5-HT1B-receptor antagonist. The selective 5-HT1 agonist, sumatriptan, had no effect in control femoral arteries, but caused a concentration-dependent contraction after PHE precontraction. These results suggest that 5-HT1-like receptors are normally inactive or "silent" in the absence of PHE. However, in the presence of PHE, these receptors become enabled and mediate the amplified response to serotonin. The evidence also suggests that, in the absence of PHE, alpha1-adrenoceptors mediated the contractile response to serotonin in the monophasic CRCs. In the biphasic curves observed late in the study, the first phase was mediated by 5-HT2A receptors, and the second, by the alpha1-adrenergic receptors.

Animals↗
PubMed1997

Diagnosis, prophylaxis, and treatment of headaches in the athlete.

BACKGROUND: Headaches are a common entity in the ambulatory population. Physicians involved in sports medicine must be able to accurately diagnose headaches in athletes and whether they are exacerbated by exertion. Many medications have proven or theoretical negative effects on athletic performance. Thus, we should consider all aspects of medical management and determine which therapy is least intrusive to the athlete's performance. We planned this review because of the small number of papers available on the effects of various medications on athletic performance. METHODS: We used MEDLINE to search from 1992 to current citations, using the medical subject headings of headache, prophylaxis, treatment, review, athletes, and exercise, alone or in combination. RESULTS: Fifty-two articles were identified and deemed appropriate for inclusion in this review. CONCLUSIONS: Acute therapy for tension headaches in the athletic population is best done with nonsteroidal anti-inflammatory drugs. Prophylaxis of chronic, recurrent tension headaches is best accomplished by night-time tricyclic antidepressants (especially nortriptyline) or selective serotonin reuptake inhibitors. Acute therapy for athletes with migraines is best managed with sumatriptan or DHE 45 and prophylaxis can be accomplished with verapamil, antidepressants, or valproate. Exertional, cluster, and structural/infectious headaches are also discussed briefly.

Analgesics, Non-Narcotic↗
PubMed1995

Treatment of cluster headache and its variants.

In cluster headache, subcutaneous administration of sumatriptan has been established as an efficient, safe and well tolerated treatment for acute attacks. For prophylactic treatment, capsaicin (intranasal administration) and leuprolide (a synthetic slow-release gonadotrophin-releasing hormone) seem to be promising. Hyperbaric oxygen therapy seems to be effective in acute attacks, but it is of interest mostly because of its apparent interruption of the cluster period in some patients. In chronic paroxysmal hemicrania, which clinically resembles cluster headache, indomethacin is still necessary for diagnosis, and it is the treatment of choice in most patients. However, because of its potential side effects, alternative treatments should be sought.

Cluster Headache↗
PubMed1999

Acute management of migraine: triptans and beyond.

Migraine is a paroxysmal disorder characterized by attacks of headache, nausea, vomiting, photophobia and phonophobia, and malaise. This review summarizes new treatment options for the therapy of acute attacks. Sumatriptan was the first specific serotonin-1B/D agonist for the treatment of acute migraine attacks. Apart from the oral and subcutaneous formulation, it is also available as nasal spray and suppository. The other new migraine drugs zolmitriptan, naratriptan, rizatriptan and eletriptan differ in their pharmacological profiles, which translates into minor differences in efficacy, headache recurrence and side-effects. Importantly, in clinical practice individual patients may show a preference for one treatment over another. New drugs in migraine treatment include substance-P antagonists, nitric oxide synthetase inhibitors and calcitonin gene-related peptide antagonists.

Humans↗
PubMed2004

Bilateral cleft lip and palate, hypertelorism and hypoplastic toes.

We report on a 23-month-old boy with bilateral cleft lip and palate, marked hypertelorism, frontal bossing and severe bilateral, asymmetric hypoplasia of toes. The mother used bisoprolol, naproxen and sumatriptan for migraine until the fifth postmenstrual week of pregnancy. We suggest that this patient's features represent a previously undescribed entity of as yet unknown aetiology.

Abnormalities, Multiple↗
PubMed2006

A model-based approach to treatment comparison in acute migraine.

AIMS: Currently, direct comparisons between 5-HT(1B/d) receptor agonists are used to assess differences and similarities in antimigraine response. Such comparisons depend on the selected sampling time and do not allow evaluation of entire response profiles. A thorough evaluation of drug properties requires that the time course of the response be taken into account. In this investigation we show the advantages of a model-based approach to compare the efficacy of two triptans (sumatriptan vs. naratriptan). METHODS: A Markov model was used to describe the course of a migraine attack over three clinically identified stages. Drug effects were modelled as concentration-dependent increases in transition rates and were parameterised as potency (EC(50)) and maximum effect (E(max)). Parameters were estimated using headache measurements from efficacy studies. Model estimates were then used to compare the pharmacodynamics of the two drugs in a time-independent manner. RESULTS: Efficacy parameters could be derived, allowing for comparison between compounds. The potency ratio (EC50(suma)/EC50(nara)) for headache relief was 3.3 (0.9, 12). The ratio of maximum effects (Emax(suma)/Emax(nara)) for this endpoint was 0.74 (0.55, 0.97). To interpret these efficacy measures and explore their value for the development of antimigraine drugs, results were evaluated against the reported in vitro potency at 5-HT(1B) and 5-HT(1D) receptors. CONCLUSIONS: Comparison of the effects of two or more drugs based on preset sampling times does not allow proper assessment of the antimigraine properties in vivo. Disease dynamics must be considered to evaluate treatment response adequately and optimise the dosing regimen in migraine.

Dose-Response Relationship, Drug↗