Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma ergotamine levels were measured in 33 volunteers (subgroups 11, 12 and 10) after a single dose of ergotamine administered by various routes. Ergotamine tartrate was given in doses normally used in the treatment of acute migraine--2.0 mg orally, 2.0 mg combined with 100 mg caffeine rectally and 0.5 mg i.m. Plasma ergotamine concentrations were determined by radioimmunoassay. The highest and longest lasting levels were found after i.m. administration, the peak concentration being 1.94 +/- 0.34 (SEM) ng/ml at 1/2 h. The corresponding maximum concentrations after oral and rectal administration were 0.36 +/- 0.08 ng/ml at 2 h and 0.42 +/- 0.09 ng/ml at 1 h. In most of the subjects the plasma ergotamine level began to rise again at 24 to 48 h. The cause of the elevation is not known but it might favour possible accumulation of the drug. Absorption from suppositories was at least as good as after oral administration and the former route may therefore be advantageous for migraine patients in whom nausea and vomiting during an attack may prevent efficient oral medication.
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PMID:Systemic availability of ergotamine tartrate after oral, rectal and intramuscular administration. 42 28

Circulating microembolic index (CMI) was determined by drawing one blood sample into EDTA-formalin and the other into DTA alone in patients with migraine and compared with matched normal controls. Platelet aggregates, if any, are fixed in EDTA-formalin but disaggregated by EDTA. Ratios of these two counts approximate "unity" in normals and are proportionately less than unity, depending on the number of platelet aggregates. 26 untreated migraineurs and 19 migraineurs with history of self-medication with aspirin taken within 72 hours of the test, were studied in headache-free intervals. Results were compared with those from 20 healthy, age and sex matched volunteers, without migraine, who were medication-free for at least one week. Mean CMI in untreated migraineurs (0.77 +/- 0.03 SEM) was significantly lower than the mean in normal controls (0.94 +/- 0.02, p. less than 0.002). Migraineurs with self administration of aspirin had mean CMI of 0.88 +/- 0.02, differing significantly from untreated migraineurs (p less than 0.01) but not from normal controls (0.1 less than p less than 0.2). Results suggest excessive platelet aggregation in migraineurs which tends to be corrected by treatment with platelet inhibitors such as aspirin.
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PMID:Platelet dysfunction in migraine: effect of self-medication with aspirin. 103 36

The steady state pharmacokinetics of propranolol was examined in 48 Saudi Arabian patients chronically treated with oral doses [mean (SEM) = 85.8 (5) mg] of this drug. The mean (SEM) of the steady state concentration (Css) per mg/kg daily dose was 21.8 (3.1) ng.ml-1/mg.kg-1. A 6-fold variability in Css was observed between patients treated with 40 mg every 8 hours and 14-fold between patients treated with 40 mg twice daily. The frequency distribution of the apparent oral clearance (TCLor) of propranolol was bimodal with 88% of the patients showing TCLor of 18 to 372 l.hr-1 while the remainder had TCLor of 471 to 749 l.hr-1. The mean (SEM) of the TCLor per kg body weight for all 48 patients was 3.16 (0.38) l.hr-1.kg-1. Both Css and TCLor obtained for Saudi Arabian patients are not significantly different from those reported for subjects from Western populations. While Css increased proportionally (P less than .001) with dosing, a near-significant (P less than .06), inverse, linear relationship was found between age and TCLor. No significant effect of sex, body weight, or disease state (i.e., heart diseases, hypertension, depression, migraine) on Css or TCLor was detected.
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PMID:Steady state pharmacokinetics of propranolol in Saudi Arabian patients and comparison with data for different populations. 231 65

Sixteen children with recurrent abdominal pain (or: "recurrent syndrome"), regarded as migraine equivalent in childhood, were submitted to the 51-Cr EDTA gut permeability test. The results were compared with those obtained in 10 healthy young adults and in 11 control children. The gut permeability in the recurrent syndrome was significantly higher than in healthy adults and control children (p less than 0.0006): The following results were obtained: 4.83 +/- 0.40 (mean +/- SEM) in the children with recurrent abdominal pain, and 2.35 +/- 0.24 2.51 +/- 0.21 in the healthy young adults and control children, respectively. The implications of these findings as far as migraine is concerned, are discussed.
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PMID:The role of the gut in migraine: the oral 51-Cr EDTA test in recurrent abdominal pain. 250 65

A parenteral formulation of dihydroergotamine (DHE) is the only galenical form now available for the treatment of acute attacks of migraine in which a rapid onset of action is required. A recently developed nasal spray of DHE has been compared with intramuscular DHE for its venoconstrictor activity. In a randomised double-blind, cross-over trial, 9 healthy male volunteers received a single dose of DHE 1 mg intranasally, DHE 0.5 mg i.m. or placebo (intranasally and i.m.) on three different occasions, with an interval of at least 1 week between doses. Both active treatments, but not placebo, produced marked venoconstriction as shown by reduced compliance of superficial hand veins. The effect persisted for more than 8 h. The maximum venoconstrictor effect of 1 mg DHE intranasally was 40 +/- 12% (mean +/- SEM) and after 0.5 mg i.m. it was 52 +/- 15%. The time course of the venoconstrictor effect was similar after both routes of administration. Blood pressure and heart rate changes in these normotensive subjects were almost identical after dihydroergotamine and placebo. The results suggest that the nasal spray could be used as an alternative to parenteral DHE, permitting self-administration of the drug for the treatment of acute attacks of migraine.
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PMID:Venoconstrictor effects of dihydroergotamine after intranasal and intramuscular administration. 375 46

The effects of ergotamine and dihydroergotamine on cerebral blood flow was investigated 4 hours after i.v. injection as these drugs might be of importance for migraine treatment. Eight normal male volunteers (not suffering from migraine) received 0.5 mg ergotamine and 1 mg dihydroergotamine i.v. Cerebral blood flow was measured by the xenon-133 inhalation method and single-photon-emission computerized tomography before and after intravenous acetazolamide administration (1 g). Cerebral blood flow was measured before and 4 hours after ergotamine and dihydroergotamine administration. Strain-gauge measurements of toe-arm systolic gradients were used to monitor the effect of the drug on leg arteries. Mean hemispheric and regional cerebral blood flow was unchanged after either drug (mean +/- SEM, ml/100 g/min): for ergotamine, 57 +/- 3 before and 57 +/- 3 at 4 hours; for dihydroergotamine, 54 +/- 2 before and 55 +/- 2 at 4 hours. The acetazolamide response was unchanged as well. Only ergotamine decreased the toe-arm systolic gradient significantly (22 mm Hg at maximum after 240 minutes; p less than 0.02). Thus, our study did not support the belief that ergot alkaloids should be withheld from patients during attacks of classic migraine, but this has to be investigated further. The discrepancy in the peripheral effects of ergotamine and dihydroergotamine might also be of clinical importance.
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PMID:The effect of ergotamine and dihydroergotamine on cerebral blood flow in man. 381 Jul 43

We have assessed the role of mefenamic acid, a non-steroidal anti-inflammatory drug known to inhibit both the synthesis and actions of prostaglandins, as an analgesic in migraine by comparing it with the established analgesic paracetamol (acetaminophen) in a double-blind cross-over trial. Forty ambulant migraine patients were supplied with oral medication for six consecutive attacks; metoclopramide 10 mg was administered in all attacks, and paracetamol 500 mg and mefenamic acid 500 mg for three attacks each. The patients recorded the intensity of the headache at the time the medication was taken, and again after 3 hours, on a linear analogue scale. Twenty-two patients completed the trial satisfactorily. Seven had insufficient attacks and the remainder were lost to follow-up. The mean reduction in headache intensity was 36 +/- 11% on mefenamic acid and 27 +/- 10% (both mean +/- SEM) on paracetamol. While this difference is not quite statistically significant (0.1 greater than P greater than 0.05) there still remains a 28% probability that mefenamic acid is twice as potent as an analgesic. The responses in each individual patient to the two drugs were very closely correlated (P much less than 0.001). Our failure to demonstrate a convincing difference between the two analgesics leads us to speculate that peripheral prostaglandin mediated pain pathways, in which paracetamol is inactive, may be less important than central pathways, which are inhibited by both drugs.
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PMID:Double blind comparison of mefenamic acid and acetaminophen (paracetamol) in migraine. 634 93

After a single-blind, 4-week placebo run-in period, 161 patients were randomized to trandolapril 2 mg once daily (n = 54), nifedipine slow-release (SR) 20 mg twice daily (n = 55), or a combination of both drugs (n = 52) for 16 weeks. Morning predosing supine diastolic blood pressure (DBP) was the primary efficacy measurement. After 16 weeks the intention-to-treat analysis showed no significant difference in supine DBP (mean +/- SEM) between trandolapril (-12.4 +/- 1.5 mm Hg) and nifedipine SR (-15.3 +/- 1.4 mm Hg; p = 0.1). However, the combination therapy was more effective (-18.9 +/- 1.3 mm Hg). Normalized blood pressure at 16 weeks was seen with 54% on trandolapril, 63% on nifedipine SR, and 77% on the combination. Adverse events, possibly related to drug, were more common with nifedipine SR (34%) than with trandolapril (17%; p < 0.05), and in comparison with the combination (21%). Drug-related treatment emergent events, reported by more than 3% of patients (fatigue, palpitations, edema, migraine), were seen only in the nifedipine SR and combination groups. Trandolapril 2 mg proved a well-tolerated and effective antihypertensive agent, comparable to nifedipine SR 40 mg. Furthermore, the combination of the two drugs was shown to enhance the antihypertensive effect of the two compounds alone. Adverse events were less common with trandolapril and the combination than with nifedipine SR alone.
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PMID:Comparison of the efficacy and safety of trandolapril and nifedipine SR in mild-to-moderate hypertension. Investigator Study Group. 752 8

This report evaluates several methods to map relative cerebral blood flow (rCBF) by applying both parametric and nonparametric techniques to deconvolve high resolution dynamic MRI measurements of paramagnetic bolus passages with noninvasively determined arterial inputs. We found a nonparametric (singular value decomposition (SVD)) deconvolution technique produced the most robust results, giving mean gray:white flow ratio of 2.7 +/- 0.5 (SEM) in six normal volunteers, in excellent agreement with recent PET literature values for age-matched subjects. Similar results were obtained by using a model-dependent approach that assumes an exponential residue function, but not for a Gaussian-shaped residue function or for either Fourier or regularization-based model-independent approaches. Pilot studies of our CBF mapping techniques in patients with tumor, stroke, and migraine aura demonstrated that these techniques can be readily used on data routinely acquired by using current echo planar imaging technology. By using these techniques, the authors visualized important regional hemodynamic changes not detectable with rCBV mapping algorithms.
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PMID:High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part II: Experimental comparison and preliminary results. 891 23

Several acutely acting antimigraine drugs, including ergotamine and sumatriptan, have the ability to constrict porcine arteriovenous anastomoses as well as the human isolated coronary artery. These two experimental models seem to serve as indicators, respectively, for the therapeutic and coronary side-effect potential of the compounds. Using these two models, we have now investigated the effects of avitriptan (BMS-180048; 3-[3-[4-(5-methoxy-4-pyrimidinyl)-l-piperazinyl[propyl]-N-methyl-l H-indole-5-methane-sulfonamide monofumarate), a new 5-HT 1B/1D receptor agonist. In anaesthetized pigs, avitriptan (10, 30, 100 and 300 micrograms.kg-1) decreased the total carotid blood flow by exclusively decreasing arteriovenous anastomotic blood flow; capillary blood flow was increased. The mean +/- SEM i.v. dose of avitriptan eliciting a 50% decrease (ED50) in the porcine carotid arteriovenous anastomotic blood flow was calculated to be 76 +/- 23 micrograms.kg-1 (132 +/- 40 nmol.kg-1) and the highest dose (300 micrograms.kg-1) produced a 72 +/- 4% reduction. In recent comparative experiments (DeVries et al. 1996), the mean +/- SEM ED50 (i.v.) of sumatriptan in decreasing carotid arteriovenous anastomotic blood flow was 63 +/- 17 micrograms.kg-1 (158 +/- 43 nmol.kg-1), with a reduction of 76 +/- 4% by 300 micrograms.kg-1, i.v. Both avitriptan (pD2; 7.39 +/- 0.09; Emax: 13.0 +/- 4.5% of the contraction to 100 mM K+) and sumatriptan (pD2: 6.33 +/- 0.09; Emax: 15.5 +/- 2.3% of the contraction to 100 mM K+) contracted the human isolated coronary artery. The above results suggest that avitriptan should be able to abort migraine headaches in patients, but may exhibit sumatriptan-like effects on coronary arteries. Initial clinical studies have demonstrated the therapeutic action of the drug in acute migraine.
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PMID:Effects of avitriptan, a new 5-HT 1B/1D receptor agonist, in experimental models predictive of antimigraine activity and coronary side-effect potential. 905 26


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