We describe two cases of palatal myoclonus (PM), one essential and another secondary to a stroke. Case 1: a 64 years old female who developed clicking sounds in both ears after a stroke and three years later on noticed a progressive involuntary movement of the throat associated with rhythmic contractions of the soft palate, muscles of tongue and throat. MRI showed an ischemic area in brainstem. The patient had a partial response to the use of sumatriptan 6 mg subcutaneously. Case 2: a 66 years old female who began with ear clicking at left ear that worsed slowly associated with tinnitus and arrhythmic movements of soft palate and an audible click at left ear. Brain MRI was normal; audiometry showed bilateral neurosensory loss. She was prescribed clonazepan 1 mg daily with complete recovery. Primary and secondary palatal myoclonus share the same clinical features but probably have different pathophysiological underlying mechanisms. (+info)
Treatment of acute migraine attacks.
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Migraine headaches are a common medical problem that physicians frequently encounter in their practice. They can be disabling, leading to the individual's suffering if not treated appropriately and quickly. There is a variety of medications and treatment approaches that can be used to relieve pain and any associated symptoms. New medications have become available in recent years to aggressively treat migraine headaches. Called "triptans," these medications have been designed to specifically treat an acute migraine attack and can be effective if used early and properly. Many medications are also available to treat symptoms associated with migraines. Patient education, along with nonpharmacologic approaches, is an element of effective treatment. Biofeedback, relaxation, and physical techniques can be effective adjunctive options. Although nonprescription medications can be helpful initially, more specific treatment is often required. Opioids, phenothiazines, ergotamine, and the triptans are generally used in patients with difficult migraines. The newer agents, the triptans, offer new hope in aggressively treating this painful condition that often has an impact on individuals and their families. (+info)
Sumatriptan elicits both constriction and dilation in human and bovine brain intracortical arterioles.
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1. Little is known about serotonin (5-HT) receptors present on brain microvessels that are innervated by brainstem serotonergic neurons. Using 5-HT, sumatriptan and subtype selective 5-HT(1) receptor agonists and/or the 5-HT(1) receptor antagonist GR127935, we characterized the 5-HT receptors involved in regulating microvascular tone of pressurized intracortical arterioles (approximately 40--50 microm) isolated from human and bovine cerebral cortex. The role of nitric oxide (NO) on these responses was assessed with the N(omega)-nitro-L-arginine (L-NNA, 10(-5) M), an inhibitor of NO synthesis. Bovine pial arteries were studied for comparative purposes. 2. At spontaneous tone, 5-HT induced a dose-dependent constriction of human and bovine microarteries (respective pD(2) values of 7.3+/-0.2 and 6.9+/-0.1); a response potently inhibited by GR127935 (pIC(50) value of 8.5+/-0.1) in bovine microvessels. 3. In both species, the 5-HT(1) receptor agonist sumatriptan induced a biphasic response consisting of a small but significant dilation at low concentrations (1 and/or 10 nM) followed by a constriction at higher doses (pD(2) for contraction of 6.9+/-0.1 and 6.6+/-0.2 in human and bovine vessels, respectively). Pre-incubation with L-NNA abolished the sumatriptan-induced dilation and significantly shifted the dose-response of the constriction curve to the left. In contrast, the selective 5-HT(1D) (PNU-109291) and 5-HT(1F) (LY344864) receptor agonists were devoid of any vasomotor effect. 4. In bovine pial vessels, 5-HT and sumatriptan elicited potent constrictions (respective pD(2) of 7.2+/-0.1 and 6.6+/-0.1), a weak dilation being occasionally observed at low sumatriptan concentrations. 5. A significant negative correlation was observed between pial and intracortical vessels diameter and the extent of the dilatory response to 10(-9) M sumatriptan. Together, these results indicate that sumatriptan, most likely via activation of distinctly localized microvascular 5-HT(1B) receptors, can induce a constriction and/or a dilation which is sensitive to inhibition of NO synthesis and dependent on the size and, possibly, the existing tone of the vessels. (+info)
pH-mediated field-amplified sample stacking of pharmaceutical cations in high-ionic strength samples.
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Capillary electrophoretic separation of samples of physiological origin typically have both poor resolution and efficiency due to destacking. We have previously reported a stacking method for concentration of catecholamines in artificial dialysate, or Ringer's solution. However, pH-mediated sample stacking of other cations has not been investigated. In this report, pH-mediated stacking has been extended to eletripan, dofetilide, doxazosin, sildenafil, UK-103,320, UK-202,581, and CP-122,288. These compounds were chosen without prior structural screening except that they were cationic at the pH of our background electrolyte (BGE). Capillary electrophoretic behavior of samples in BGE is compared with those of samples in Ringer's solution with and without pH-mediated acid stacking. Results indicate that the peak heights and efficiencies for acid-stacked samples are increased compared to the unstacked samples in Ringer's solution or BGE. For example, the peak efficiencies for 5 s injections of eletriptan in BGE and Ringer's solution are 138,000 and 72,000 plates, respectively. In contrast, a 10 s injection of eletriptan followed by acid injection for 16 s produces a peak with 246,000 plates. Evaluation of the stacking effect was performed by comparison of the peak height at similar peak efficiencies for samples in Ringer's solution with and without stacking. Using this method, pH-mediated acid stacking provides a 10- to 27-fold sensitivity enhancement for the seven cations. (+info)
Comparative effects of frovatriptan and sumatriptan on coronary and internal carotid vascular haemodynamics in conscious dogs.
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The effects of frovatriptan and sumatriptan on internal carotid and coronary vascular haemodynamics were investigated and compared in conscious dogs. Frovatriptan and sumatriptan (0.1 - 100 microg kg(-1)) induced a transient increase in external coronary artery diameter (eCOD) of up to 2.9+/-1.2 and 1.8+/-0.6%, respectively (both P:<0.05). This was followed by a prolonged and dose-dependent decrease in eCOD of up to -5.2+/-1.2 and -5.3+/-0.9% (both P:<0.05), with ED(50) values of 86+/-21 and 489+/-113 micromol kg(-1), respectively. In contrast, only a decrease in the external diameter of the internal carotid artery was observed (-6.0+/-0.6 and -6.2+/-1.4%, both P:<0.05, and ED(50) values of 86+/-41 and 493+/-162 micromol kg(-1), respectively). Frovatriptan was thus 5.7 fold more potent than sumatriptan at the level of both large coronary and internal carotid arteries. After endothelium removal by balloon angioplasty in coronary arteries, the initial dilatation induced by the triptans was abolished and delayed constriction enhanced. The selective antagonist for the 5-HT(1B) receptors SB224289 dose-dependently blocked the effects of sumatriptan on large coronary and internal carotid arteries whereas the selective antagonist for the 5-HT(1D) receptors BRL15572 did not affect any of these effects. In conclusion, frovatriptan and sumatriptan initially dilate and subsequently constrict large coronary arteries in the conscious dog, whereas they directly constrict the internal carotid artery. The vascular endothelium modulates the effects of these triptans on large coronary arteries. Finally, 5-HT(1B) but not 5-HT(1D) receptors are primarily involved in canine coronary and internal carotid vasomotor responses to sumatriptan. (+info)
Serotonin-induced hypercontraction through 5-hydroxytryptamine 1B receptors in atherosclerotic rabbit coronary arteries.
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BACKGROUND: Augmented vasoconstriction to serotonin (5-hydroxytryptamine [5-HT]) in atherosclerotic vessels plays a crucial role in the development of myocardial ischemia. We investigated mechanisms for serotonin-evoked hypercontraction in atherosclerotic rabbit coronary arteries. METHODS AND RESULTS: Contractile responses to serotonergic agents of endothelium-denuded coronary arteries from control and Watanabe heritable hyperlipidemic rabbits (WHHL) were examined. WHHL coronary arteries exhibited hypercontraction to 5-HT(1)-receptor agonists; the constrictor threshold concentrations and E:D(50) to serotonin, 5-carboxamidotryptamine, and sumatriptan in WHHL were significantly lower, and the E:(max) in WHHL to these agents were increased 55% to 59% above those of the control. Serotonin-evoked contractions in both groups were inhibited by GR127935 (5-HT(1B/1D) antagonist; 0.1 to 1 nmol/L) and pertussis toxin but not by ketanserin (5-HT(2) antagonist; 0.01 to 1 micromol/L), suggesting that the hypercontraction is most likely mediated by 5-HT(1B/1D) receptors through a pertussis toxin-sensitive pathway. Furthermore, simultaneous measurements of [Ca(2+)](i) and isometric tension of fura-2-loaded arteries revealed that the hypercontraction was concomitant with the augmented elevation of [Ca(2+)](i) in the smooth muscle. The 5-HT(1B) mRNA levels in WHHL coronary arteries increased to 2.5-fold over those in control arteries, whereas neither 5-HT(1D) nor 5-HT(2A) mRNA was detected in either group. CONCLUSIONS: Atherosclerotic rabbit coronary arteries exhibited the enhancement in contraction and Ca(2+) mobilization in response to serotonin. The 5-HT(1B) receptor, which is upregulated by atherosclerosis, most likely mediates the augmenting effects of serotonin. (+info)
Adenosine A(1) receptor-mediated inhibition of protein kinase A-induced calcitonin gene-related peptide release from rat trigeminal neurons.
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Calcitonin gene-related peptide (CGRP), a potent vasodilator, has been implicated in the pathogenesis of migraine. Its release from adult rat trigeminal neurons in culture was shown to be markedly increased by the activation of adenylate cyclase with forskolin. Modulation of this secretion was investigated by a number of agents with known inhibitory effects on cAMP generation mediated via receptor coupling to G(i/o) proteins. Significantly, forskolin-stimulated CGRP release could be closely correlated with the phosphorylation of the protein kinase A (PKA) substrate cyclic AMP response element-binding protein (CREB). Forskolin-stimulated CGRP release could be potently and effectively inhibited by the adenosine A(1) receptor-selective agonist GR79236X (pIC(50) = 7.7 +/- 0.1, maximal inhibition 65 +/- 2.5% at 300 nM), whereas the A(2A) (CGS21680) and the A(3) (2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide) receptor-selective agonists were without effect. GR79236X-mediated inhibition was abolished by the A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine. Immunocytochemical studies and Western analysis revealed the presence of adenosine A(1) receptors on trigeminal neurons. However, despite the additional detection of 5-hydroxytryptamine (5-HT)(1B) receptors on these cells, the clinically effective antimigraine 5-HT(1B/1D) agonist sumatriptan did not inhibit forskolin-stimulated CGRP release nor did it show any effect on the concomitant CREB phosphorylation. In contrast, the mu-opioid agonist fentanyl elicited a 74 +/- 4% reduction in CGRP levels. Forskolin-stimulated CGRP release and CREB phosphorylation could be mimicked by incubation of the cells with chlorophenylthio-cAMP and blocked by pretreatment with the PKA inhibitor myrPKI(14-22). Taken together, the present data confirm the PKA-dependence of forskolin-stimulated CGRP release and suggest that A(1) adenosine agonists may warrant further investigation in models of migraine and neurogenic inflammation. (+info)
Dexamethasone decreases migraine recurrence observed after treatment with a triptan combined with a nonsteroidal anti-inflammatory drug.
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BACKGROUND AND OBJECTIVES: Triptans are effective drugs for the acute treatment of migraine. However, 30-40% of the patients commonly present recurrence before 24 hours therefore requiring another dose. Nonsteroidal anti-inflammatory drugs (NSAID) such as tolfenamic acid and naproxen sodium combined with sumatriptan have demonstrated efficacy in reducing recurrence observed with the single use of this drug. Steroids also have been suggested to treat refractory migraine and status migranosus. The aim of this study was to evaluate whether patients presenting frequent recurrence with the combination triptan plus NSAID, would decrease it with the association of dexamethasone. METHOD: Twenty three patients, 17 women and 6 men with migraine according to IHS criteria were prospectively studied. All patients presented frequent recurrence (> or= 60%, mean recurrence rate 74,8%) with the single use of sumatritpan 100 mg or zolmitriptan 2,5 mg or rizatriptan 10mg in at least 5 consecutive attacks, and didn't present a reduction of the recurrence rate superior than 20% with the combination of tolfenamic acid 200 mg or rofecoxib 25 mg in at least 5 other consecutive attacks (mean recurrence rate 60%). The patients had to treat 6 consecutive moderate or severe migraine attacks with their usual combination plus 4 mg of dexamathasone with a maximum of twice a week, and fill out a diary reporting headache parameters. RESULTS: Twenty patients, 16 women and 4 men completed the study. Of those who completed the study, 11 took rizatriptan plus rofecoxib, 4 rizatriptan plus tolfenamic acid, 3 zolmitriptan plus rofecoxib, 1 zolmitriptan plus tolfenamic acid and 1 patient took sumatriptan plus tolfenamic acid, having the 20 patients taken as a third medication, a single tablet of 4 mg of dexamethasone. All patients took oral formulations and none presented vomiting after that. Among all 20 patients, one female and one male patient presented recurrence in 3 out of the 6 attacks (50%) while the remaining 18 patients revealed recurrence in 1 or 2 treated attacks (mean 23,4%) (p<0,001). CONCLUSION: We concluded that the judicious use of oral dexamethasone might be useful for a limited population of migraine patients still presenting recurrence with the combination of a triptan and a NSAID. Case-control studies and studies with a randomized double-blind design are necessary to confirm these observations. (+info)