benzofurans and Migraine-Disorders

Topics: Benzofurans; Benzoxepins; Drug Administration Schedule; Humans; Migraine Disorders

Topics: Benzofurans; Benzoxepins; Double-Blind Method; Drug Evaluation; Humans; Migraine Disorders; Vascular Headaches

Topics: Benzofurans; Benzoxepins; Drug Administration Schedule; Drug Evaluation; Female; Humans; Migraine Disorders

Topics: Adolescent; Adult; Benzofurans; Benzoxepins; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Male; Middle Aged; Migraine Disorders; Placebos

A selective liquid chromatographic-mass spectrometric method has been developed and validated for simultaneous determination of senkyunolide I (SEI) and senkyunolide H (SEH) from Chuanxiong Rhizoma in rat plasma. Plasma samples were extracted by liquid-liquid extraction with ethyl acetate and separated on a Kromasil C18 column (250 × 4.6 mm, 5 µm), with methanol-water (55:45, v/v) as mobile phase. The linear range was 0.05-25 µg/mL for SEI and 0.01-5.0 µg/mL for SEH, with lower limits of quantitation of 0.05 and 0.01 µg/mL, respectively. Intra- and inter-day precision were within 10.0 and 9.8%, and the accuracies (relative errors) were <9.6 and 5.9%, with the mean extraction recoveries 81.0-86.6 and 80.5-85.0% for the two anayltes, respectively. The validated method was successfully applied to a comparative pharmacokinetic study of SEI and SEH in normal and migrainous rats after oral administration of Chuanxiong Rhizoma extract. The results indicated that there were obvious differences between normal and migrainous rats in the pharmacokinetic behavior after oral administration of Chuanxiong Rhizoma extract. The absorption of SEI and SEH were significantly increased in migrainous rats compared with normal rats.

Topics: Administration, Oral; Animals; Benzofurans; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Humans; Ligusticum; Male; Migraine Disorders; Rats; Rats, Sprague-Dawley; Rhizome; Tandem Mass Spectrometry

Senkyunolide I is an active ingredient of Rhizoma Chuanxiong, a Chinese medicinal herb commonly used for the treatment of cardiovascular ailments. In the present paper, we describe the isolation and elucidation of senkyunolide I from the ethanol extract of Rhizoma Chuanxiong and its pharmacokinetic behavior after intravenous and oral administration to normal and migrainous rats. After intravenous administration, senkyunolide I was rapidly distributed (V ( z )/F 2.07 ± 0.43 L/kg) and eliminated from the plasma (CL( z ) 2.56 ± 0.29 L/h/kg and t (1/2z ) 0.56 ± 0.13 h). After administration orally to normal rats at two dosages (20 and 72 mg/kg), the pharmacokinetic parameters of senkyunolide I were as follows: T (max) 0.25 ± 0.06 and 0.38 ± 0.11 h, C (max) 5,236.3 ± 802.8 and 22,071.9 ± 3,456.1 mg/L, Area under the curve(AUC)((0-t)) 5,217.5 ± 1,029.5 and 21,480.2 ± 3,003.1 μg h/L, respectively. Its oral absolute bioavailability at the two dosages was 67.2 and 76.9%, respectively. Intriguingly, migraine caused some significant changes in its pharmacokinetic parameter. For example, when compared with its pharmacokinetic behavior in normal rats at the two dosages, on average, its clearance decreased by 68% and volume of distribution increased by 342% in migrainous rats, both of which contributed to its several-fold increase in t (1/2z) and AUC. C (max) and AUC of senkyunolide I increased almost proportionally with dose between 20 and 72 mg/kg and the pharmacokinetics fit linear kinetic feature. The pharmacokinetic parameters of senkyunolide I were significantly different in normal and migrainous rats, which should be taken into account during the design of a clinical dosage regimen for senkyunolide I.

Topics: Administration, Oral; Animals; Area Under Curve; Benzofurans; Chromatography, High Pressure Liquid; Disease Models, Animal; Dose-Response Relationship, Drug; Half-Life; Injections, Intravenous; Male; Migraine Disorders; Rats; Rats, Sprague-Dawley; Tissue Distribution

To evaluate the analgesic and anti-migraine activities of senkyunolide I from Ligusticum chuanxiong.. Mice were orally administered various doses of senkyunolide I, and their pain levels were assessed in a hot-plate test and by application of acetic acid. The levels of 5-hydroxytryptamine (5-HT), 5-hydroxytryptophan (5-HTP), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE) and dopamine (DA) in plasma and brain were assessed, and the monoamine turnover rates (5-HT/5-HTP, 5-HIAA/5-HT and NE/DA) were also calculated.. Mice given senkyunolide I at 16 and 32 mg/kg had significantly elevated pain thresholds in the hot-plate test, and a dose of 32 mg/kg also reduced the number of abdominal writhing responses caused by acetic acid. Significant improvements were observed in the neurotransmitter levels of the drug-treated rats compared with the saline-administered controls. Compared to the rats with nitroglycerin-induced migraines, the levels of nitric oxide in the plasma and whole brain of rats given senkyunolide I were lower.. The present study suggests that senkyunolide I may be an active component of L. chuanxiong, traditionally used to treat migraine. The mechanism of pain relief in migraine model rats may be through adjusting the levels of monoamine neurotransmitters and their turnover rates, as well as decreasing nitric oxide levels in the blood and brain. Therefore, senkyunolide I may be developed as a potential treatment for migraine pain.

Topics: 5-Hydroxytryptophan; Acetates; Analgesics; Animals; Benzofurans; Brain; Dopamine; Drugs, Chinese Herbal; Hydroxyindoleacetic Acid; Ligusticum; Mice; Migraine Disorders; Neurotransmitter Agents; Nitric Oxide; Nitroglycerin; Norepinephrine; Pain Threshold; Rats; Rats, Sprague-Dawley; Serotonin

Topics: Adult; Animals; Benzofurans; Bridged Bicyclo Compounds, Heterocyclic; Clinical Trials, Phase II as Topic; Half-Life; Humans; Male; Migraine Disorders; Serotonin Antagonists

Topics: Adult; Benzofurans; Benzoxepins; Drug Evaluation; Female; Headache; Humans; Male; Middle Aged; Migraine Disorders; Vascular Headaches

Topics: Adolescent; Adult; Benzofurans; Benzoxepins; Drug Evaluation; Female; Headache; Humans; Male; Migraine Disorders; Vascular Headaches