endothelin-1 and Headache

Author presents new epidemiological data in prevalence of headaches in children and adolescents. She precises tension headaches and pathogenesis of migraine and reminds difficulties in its differentiation. She points out to endothelin-1 importance in this process.

Topics: Adolescent; Age Distribution; Child; Diagnosis, Differential; Electroencephalography; Endothelin-1; Headache; Humans; Migraine Disorders; Prevalence; Tension-Type Headache

The purpose of this study was to investigate in healthy male subjects the tolerability, pharmacokinetics, and pharmacodynamics of ascending doses of clazosentan, an intravenous endothelin receptor antagonist.. Clazosentan was infused at doses of 3-60 mg/h for 3 h, 60 mg/h for 6 h and at 30 mg/h for 12 h. Each dose was given to a separate group of subjects, six of whom received clazosentan and two placebo. Vital signs, ECG, adverse events, and clinical laboratory variables were monitored to assess tolerability. Blood and urine samples were collected frequently for pharmacokinetic and pharmacodynamic determinations.. Infusion of clazosentan up to doses of 30 mg/h for 3 h was well tolerated. A dose of 60 mg/h and longer infusions were less well tolerated and three subjects did not complete the 12-h infusion of 30 mg/h due to adverse events. Headache was the most commonly reported adverse event followed by nausea, vomiting, and nasal congestion. The pharmacokinetics of clazosentan were dose proportional in the dose range investigated. Values (mean and 95% confidence intervals) for clearance and volume of distribution at a dose of 10 mg/h for 3 h were 42.2 (36.6, 48.7) l/h and 32.4 (27.0, 38.8) l, respectively. Both variables were independent of dose. The elimination of clazosentan was characterized by a very rapid disposition phase with a half-life of 6-10 min. Compared to baseline, endothelin-1 concentrations increased approximately 2-fold after infusion of clazosentan but no dose-dependent relationship could be discerned for this effect.. The observed tolerability, pharmacokinetic, and pharmacodynamic profile warrant further clinical development of clazosentan at lower doses.

Topics: Adult; Blood Pressure; Chromatography, Liquid; Dioxanes; Dose-Response Relationship, Drug; Double-Blind Method; Endothelin A Receptor Antagonists; Endothelin-1; Half-Life; Headache; Humans; Infusions, Intravenous; Male; Nasal Obstruction; Nausea; Pyridines; Pyrimidines; Sulfonamides; Tetrazoles; Tissue Distribution; Vomiting

Individuals with migraine present ictal elevation of endothelin-1 levels. Migraine can be subclassified into episodic migraine and chronic migraine. Apart from the inconsistent reports on interictal endothelin-1 levels, most studies did not distinguish between episodic migraine and chronic migraine.. We measured plasma endothelin-1 levels in participants with episodic migraine (n = 87), with chronic migraine (n = 88), and controls (n = 50).. Interictal endothelin-1 levels were not significantly different among participants with episodic migraine, those with chronic migraine, and controls (pg/ml, median and interquartile range, 10.19 [7.76-13.69] vs. 9.25 [6.91-10.73] vs. 9.46 [7.00-14.19],. Interictal plasma endothelin-1 level is an unlikely marker for episodic migraine and chronic migraine.

Topics: Biomarkers; Endothelin-1; Headache; Headache Disorders, Secondary; Humans; Migraine Disorders