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Background Racemic isometheptene [(RS)-isometheptene] is an antimigraine drug that due to its cardiovascular side-effects was separated into its enantiomers, (R)- and (S)-isometheptene. This study set out to characterize the contribution of each enantiomer to its vasoactive profile. Moreover, rat neurogenic dural vasodilatation was used to explore their antimigraine mechanism of action. Methods Human blood vessel segments (middle meningeal artery, proximal and distal coronary arteries, and saphenous vein) were mounted in organ baths and concentration response curves to isometheptene were constructed. Calcitonin gene-related peptide (CGRP)-induced neurogenic dural vasodilation was elicited in the presence of the enantiomers using a rat closed cranial window model. Results The isometheptene enantiomers did not induce any significant contraction in human blood vessels, except in the middle meningeal artery, when they were administered at the highest concentration (100 μM). Interestingly in rats, (S)-isometheptene induced more pronounced vasopressor responses than (R)-isometheptene. However, none of these compounds affected the CGRP-induced vasodilator responses. Conclusion The isometheptene enantiomers displayed a relatively safe peripheral vascular profile, as they failed to constrict the human coronary artery. These compounds do not appear to modulate neurogenic dural CGRP release, therefore, their antimigraine site of action remains to be determined.

Background The main treatments in a majority of headache patients are pharmacologic therapies. As a result, it is imperative to have strong background in pharmacotherapy used to treat headaches in order to provide optimal therapy and avoid drug interactions. One of the main reasons for failure of pharmacologic treatment of headaches is drug–drug interactions (DDIs). While there are many distinct pathways and mechanisms in which DDIs can occur, most occur through alterations within the cytochrome P450 pathways (CYP). Drugs that cause induction, inhibition, or are simply substrates for these pathways are responsible for many of the DDIs. Aim/Results We review and discuss the important and potential DDIs of commonly used headache medication often encountered in clinical practice. We divide the drugs into two classes, abortive and preventive. Within each group we select the most commonly used drugs and provide a detailed discussion of the mechanisms of interaction for each. Also included are commonly used herbal supplements, which can interact with headache medications. Conclusion Drug–drug-interactions are a major concern when developing a treatment regimen for patients suffering from headaches. There is a growing need for physician attention to the pharmacokinetics of drugs to improve the quality of patient care. It is vital that prescribing physicians be aware of the DDIs associated with the commonly prescribed headache medications to optimize patient care and therapy results.

Patients and physicians consider rapid onset of pain relief and pain freedom among the most important attributes of migraine therapy.This study compared the effectiveness of rizatriptan 10 mg and usual-care oral migraine medications in everyday clinical practice settings.This was a multicenter, prospective, open-label study. Adult patients treated 2 sequential migraine attacks with rizatriptan 10 mg and a usual-care prescription migraine medication in a crossover manner. Patients chose which medication to take first. They recorded the treatment outcomes using a stopwatch and a treatment diary. End points included time to pain freedom (length of time from dosing to no pain) and time to onset of pain relief (mean time to onset of pain relief and proportion of patients reporting onset of pain relief at 30 minutes), satisfaction with treatment, and medication preference. Information on adverse events was collected through the normal post-marketing reporting mechanism. Comparisons were made using the paired t test and McNemar test for continuous and categorical variables, respectively. A mixed model, accounting for multiple observations per patient, was fitted for the time to pain freedom, controlling for age, sex, treatment period, medication, and headache severity.Of 2346 enrolled patients, 1489 treated 2 migraines in a crossover manner and were included in the analysis (86.8% women, 13.2% men; mean age, 41.7 years). A majority of patients (80.6%) treated both migraines with oral triptans. The most commonly used nontriptans were NSAIDs (5.4%), butalbital-containing combinations (4.3%), and isometheptene (3.4%). Over-the-counter medications were used by 22.3% of patients during rizatriptan-treated attacks and by 28.9% of patients during attacks treated with usual-care medications. The mean time to pain freedom was significantly shorter when an attack was treated with rizatriptan compared with usual-care medications (222 vs 298 minutes, respectively; P0.001), and the onset of pain relief was significantly more rapid (85 vs 107 minutes; P=0.003), with significant differences noted as early as 15 minutes after dosing (P0.001). The findings remained similar after adjustment for potential confounding factors. No significant sequence effect was detected. Significantly more patients reported being very satisfied or satisfied with rizatriptan compared with usual-care medications (65.4% vs 57.7%; P0.001) and preferred rizatriptan (58.0% vs 42.0%; P0.001). One female patient reported having hives and itchy skin the day after taking rizatriptan; the symptoms subsided after treatment with methylprednisolone.In this selected population, treatment of a migraine attack with rizatriptan 10 mg was associated with a faster time to pain freedom and onset of pain relief compared with treatment with usual-care oral migraine medications. Patients reported greater satisfaction with and preference for rizatriptan.

A study of the metabolism of isometheptene, an antispasmodic drug, in man and comparison with heptaminol metabolism, is presented in this paper. Isometheptene and two metabolites were detected in human urine after oral administration of a tablet containing isometheptene mucate. The urine level of the parent drug, which is excreted during the first 24 h, was determined using gas chromatography-mass spectrometry, after alkaline extraction with organic solvent. A minor metabolite of isometheptene was converted to heptaminol in vitro under the acidic hydrolysis conditions used for the screening procedure of stimulants and narcotics in doping control analysis.

The treatment of migraine headache is often suboptimal despite significant advances in our understanding of the pathophysiology and treatment of migraine. Children, adolescents, women and the elderly are particularly at risk of receiving inadequate or inappropriate therapy. In this review, the reader is brought up-to-date with changes to the International Headache Society diagnostic criteria for migraine. The pathophysiology of migraine is also reviewed, with a special emphasis on the evolving concept of central sensitization and cutaneous allodynia since this concept has led to a paradigm shift in the way migraines are managed. A review of the evidence supporting the benefits of early treatment before pain becomes moderate-to-severe is provided. Recommendations for acute and prophylactic treatments throughout the lifecycle are made in light of clinical practice guidelines and more recent evidence. Lastly, the current optimal treatment of migraine is provided and the potential role of calcitonin gene-related peptide antagonists in the future is discussed.

Background: Migraine headache is associated with significant costs. Many patients with migraine do not receive appropriate care. Correct diagnosis of migraine is often elusive, which may impact patient care. Objective: To determine the economic and disability burdens that patients with migraine experience before treatment and after diagnosis and treatment. Methods: This survey was administered to patients in a community pharmacy. Eligible patients were 18–40 years of age with diagnosed migraine who had prescriptions for an ergotamine, triptan, or combination product containing acetaminophen, isometheptene, and dichloralphenazone. Main outcome measures included pre- and postdiagnostic comparison of patient disability measures, migraine medication use, migraine-related patient costs, and physician office visit characteristics and diagnostic testing. Results: Forty-nine patients completed the study (mean ± SD age 38 ± 14 y, 90% female). The average age of symptom onset was 24 ± 13 years, with first presentation to physician at age 28 ± 12 and diagnosis made at age 31 ± 12 years. The mean number of physicians visited was 2.3 ± 4.7, comprising 5.3 ± 7.8 office visits before diagnosis. After diagnosis and treatment, significantly fewer patients experienced attacks lasting ≥16 hours and reported missing ≥5 days of work/month from migraine symptoms. Patients also reported significantly increased effectiveness at work when experiencing symptoms after diagnosis and treatment. Conclusions: This study demonstrated that migraine often eludes formal diagnosis and diagnosis is difficult for the primary care physician to make without expensive tests and/or consultation. Patient outcomes were greatly improved after a formal diagnosis followed by appropriate treatment.

The present study set out to investigate the pharmacological profile of the cardiovascular responses induced by the antimigraine agent, isometheptene, in pithed rats. For this purpose, intravenous (i.v.) administration of blocking doses of the antagonists prazosin (alpha1; 100 microg/kg), rauwolscine (alpha2; 300 microg/kg), the combination of prazosin (100 microg/kg) plus rauwolscine (300 microg/kg), propranolol (beta; 1000 microg/kg), ritanserin (5-HT2; 100 microg/kg) or equivalent volumes of saline (1 ml/kg) were used. Isometheptene (0.03, 0.1, 0.3, 1 and 3 mg/kg, i.v.) produced dose-dependent increases in heart rate and diastolic blood pressure which were highly reproducible as they remained unaltered after saline. These tachycardic responses to isometheptene remained unaffected after prazosin, rauwolscine, ritanserin or the combination prazosin plus rauwolscine, but were abolished after propranolol. In contrast, the isometheptene-induced vasopressor responses were not significantly modified after the above doses of rauwolscine, ritanserin or propranolol, but were markedly blocked after prazosin or the combination of prazosin plus rauwolscine; the latter blockade did not significantly differ from that produced by prazosin alone. Interestingly, in rats pretreated intraperitoneally (i.p.) with reserpine (5 mg/kg; -24 h), isometheptene-induced tachycardic responses were abolished whereas the corresponding vasopressor responses were markedly attenuated and subsequently blocked by prazosin. It is concluded that isometheptene-induced tachycardic responses seem to involve only an indirect (tyramine-like action) mechanism mediated by beta-adrenoceptors, whilst the corresponding vasopressor responses are mediated by a predominantly indirect (tyramine-like action), as well as a minor direct (alpha1-adrenoceptors), sympathomimetic mechanism.

Study Objective: To compare the recovery characteristics of two widely used anesthetic techniques: remifentanyl-propofol and sevoflurane-fentanyl in a standardized ambulatory population. Design: Randomized, single-blinded study. Setting: University-affiliated medical center. Patients: 50 ASA physical status I and II patients undergoing elective ambulatory otorhinolaryngeal surgery. Interventions: Patients were randomized two groups to receive total intravenous anesthesia (TIVA group) with remifentanil and propofol or sevoflurane-fentanyl (SF group). TIVA patients received induction with propofol 1.5 mg/kg intravenously (IV) and remifentanil 0.5 ?/kg IV. The anesthesia was continued with a continuous infusion of propofol 100 ?g/kg/min and remifentanil 0.0625-0.25 ?g/kg/min. The SF group received, at induction, fentanyl 2 ?g/kg followed by propofol 1.5 mg/kg IV. Maintenance was obtained with 1 to 1.5 minimum alveolar concentration of sevoflurane and bolus of fentanyl 1 ?g/kg IV as needed. Measurements and Main Results: Early recovery times (eye opening, response to commands, extubation, orientation, operating room stay after surgery, and Aldrete score ?9) and patient satisfaction were similar between the two groups. Postanesthetic discharge scoring system (PADSS) ? 9 was significantly shorter for the TIVA group (135.9 ± 51 vs. 103 ± 32 min) (p less than 0.01) but this difference was not associated with a shorter postanesthesia care unit (PACU) length of stay. Conclusion: Early recovery times are comparable between total intravenous anesthesia and sevoflurane-based anesthesia. Even though patients in the TIVA group achieved home readiness criteria in a significantly shorter time, this technique does not shorten PACU length of stay, which depends instead on multiple nonmedical and administrative issues. © 2002 by Elsevier Science Inc.

Migraine is a common and disabling disease of uncertain pathogenesis. Research on the trigeminovascular system, serotonin receptors, and substance P have provided clues to improving the pharmacotherapy of this disorder. Selective serotonin agonists, such as sumatriptan, dihydroergotamine, ergotamine tartrate, nonsteroidal anti-inflammatory drugs (NSAIDS), isometheptene mucate, and phenothiazines are useful to treat acute attacks. Prophylactic agents include beta-blockers, calcium channel blockers, NSAIDs, antidepressants, and valproate. The addition of several new agents for the acute and prophylactic therapy of migraine has improved the outlook for this debilitating disorder.

The efficacy and tolerability of a combination of dipyrone 600 mg, isometheptene 60 mg and caffeine 60 mg for the acute treatment of mild-to-moderate episodic primary headaches were evaluated against paracetamol 1000 mg and placebo. A total of 84 adult patients with two to six primary headache episodes (mild or moderate severity) per month were enrolled in this prospective, multicenter, randomized, two-period crossover study. Patients had a mean of 4.4 headache episodes/month (mean duration: 13 h; mean severity: 50.5 mm; assessed by visual analog scale (VAS). In patients with no improvement, rescue medications were allowed after 2 h. The primary outcome parameter was sustained pain-free rate. Secondary outcomes were evolution of pain severity (at 30, 60, 90, 120 and 240 min after treatment), presence of associated symptoms, and recurrence of episodes. Analyses included 243 headache episodes (81 patients). Sustained pain-free rates were 57.1% for combination therapy, 46.8% for paracetamol and 46.8% for placebo (not statistically significant). Pain improvement (assessed by VAS) occurred in 72.5, 54.5 and 49.2% of patients, respectively, after 120 min. The mean reduction in pain severity (assessed by VAS) was significantly lower in those receiving placebo and paracetamol compared with combination therapy (p < 0.001 at 90 and 120 min). Fewer patients required rescue medication after receiving combination therapy (18.4%), compared with paracetamol (37.7%; p = 0.008) or placebo (43.8%; p = 0.0007). Adverse events were infrequent and mild. We conclude that, despite failing to meet the primary outcome, the combination of dipyrone, isometheptene and caffeine is effective for the acute treatment of mild-to-moderate primary headache episodes, with excellent tolerability.

Objective The purpose of this case report is to describe the chiropractic management of a 39-year-old woman with essential tremors and migraine headaches. Clinical Features A 39-year-old woman presented with essential tremors and migraine headaches, which occurred 2 to 3 times per week. The essential tremor was diagnosed in 2000, and migraine headaches with aura were diagnosed when she was 10. Both diagnoses were made by her general medical practitioner. Previous treatments for migraine included propranolol, isometheptene, dichloralphenazone, acetaminophen, sumatriptan, and over-the-counter pain relievers. Intervention and Outcome The patient received high-velocity, low-amplitude chiropractic spinal manipulation to her upper cervical spine using the Blair Upper Cervical chiropractic technique protocol. There was improvement in her tremors and migraine headaches following her initial chiropractic treatment, with a sustained improvement after 4 months of care. Conclusion This case study demonstrated improvement in a woman with essential tremors and migraine headaches. This suggests the need for more research to examine how upper cervical specific chiropractic care may help mitigate tremors and migraine headaches.

A 45 year old female with no stroke risk factors suffered a massive intracerebral hemorrhage (ICH) after ingesting Midrin – a combination of isometheptene mucate, dichlorophenazine and acetaminophen. Neuroimaging revealed no evidence of structural disease or underlying vasculopathy. This is the first reported case of isometheptene induced ICH in the absence of underlying cerebrovascular disease. Physicians must be aware of the potential for this complication, and inquire about the use of isometheptene in unexplained cerebral hemorrhages. Neurological communities in countries with nonprescription isometheptene should discourage unsupervised or excessive use of the drug.

Background.—Migraine affects people of all races and both sexes. Migraineurs suffer both financial losses and impaired quality of life. Recent progress in the treatment of migraine has not been made readily available to all who suffer the condition. Objective.—To assess outpatient health care delivery patterns for migraine sufferers in the United States. Methods.—National Ambulatory Medical Care Survey data from 1990 to 1998 was used to assess the demographics of patients seen with a diagnosis of migraine, the types of physicians they saw, and the medications used to treat migraine. Results.—Women accounted for 79% of visits for migraines and whites for 91% of the visits. There was a dramatic increase in the number of migraine visits during the study period, from 9.4 visits per 1000 people in 1990 to 18 visits per 1000 in 1998. Primary care physicians saw the majority of patients (72.2%). Butalbital/aspirin/caffeine was the drug most commonly prescribed for migraine treatment, followed by acetaminophen/dichloralphenazone/isometheptene mucate, propranolol, and sumatriptan. Conclusion.—Perhaps in part due to newer treatment options, the number of visits for the treatment of migraine doubled over the study interval. Even so, most patients with migraine continue to be treated with older and presumably less effective medications.

The present study set out to investigate the external carotid vascular effects of isometheptene in vagosympathectomised dogs, anaesthetised with pentobarbital. One-minute intracarotid (intra-arterial; i.a.) infusions of isometheptene (10, 30, 100 and 300 microg/min) produced dose-dependent decreases in external carotid blood flow, without affecting blood pressure or heart rate. The vasoconstrictor responses to 100 microg/min and 300 microg/min of isometheptene were clearly attenuated in animals pretreated with reserpine (5,000 microg/kg). Moreover, after prazosin (an alpha1-adrenoceptor antagonist; 100 microg/kg), the responses to isometheptene remained unaltered in untreated as well as reserpine-pretreated dogs. In contrast, the responses to isometheptene were attenuated by rauwolscine (an alpha2-adrenoceptor antagonist; 300 microg/kg) in untreated animals, and were practically abolished in reserpine-pretreated dogs. Further investigation into the specific alpha2-adrenoceptor subtypes, using selective antagonists, showed that BRL44408 (alpha2A) and MK912 (alpha2C) markedly attenuated this response, while imiloxan (alpha2B) was ineffective. The involvement of 5-HT1B and 5-HT1D receptors seems highly unlikely since antagonists at 5-HT1B (SB224289) and 5-HT1D (BRL15572) receptors (both at 300 microg/kg) were ineffective. On this basis, it is concluded that isometheptene-induced canine external carotid vasoconstriction is mediated by both indirect (a tyramine-like action) and direct (acting at receptors) mechanisms, which mainly involve alphaA- and alpha2C-adrenoceptors, while the involvement of alpha1-adrenoceptors seems rather limited.

Objective To describe a patient who developed reversible segmental cerebral arterial vasospasm and cerebral infarction while taking excessive amounts of sumatriptan succinate and a combination drug (Midrin) consisting of isometheptene mucate, 65 mg, dichloralphenazone, 100 mg, and acetaminophen, 325 mg. Design Case report. Setting Tertiary care center. Patient A 43-year-old man who developed a left occipital infarct after taking a total of 23 sumatriptan succinate tablets (25 mg per tablet) and 32 Midrin tablets during a 7-day period and who on digital subtraction angiography was shown to have segmental cerebral arterial narrowing in multiple vessels. An extensive evaluation for other possible risk factors for cerebral infarction was unrevealing. Main Outcome and Results Discontinuation of sumatriptan and Midrin regimens and administration of nicardipine hydrochloride led to nearly total resolution of the angiographic findings, and the patient had no recurrent strokes. Conclusions One should consider the diagnosis of drug-induced vasospasm in patients with cerebral infarction and a history of excessive use of sumatriptan and Midrin. The initial angiographic abnormalities may resemble those found in patients with primary angiitis of the central nervous system.

Publisher Summary This chapter discusses drugs affecting autonomic functions or the extrapyramidal system. A report describes an autonomic dysreflexic syndrome following the use of an isometheptene combination to treat migraine. Repeated use of an oxymetazoline nasal spray has been associated with changes in fetal heart rate demonstrated as a non-reactive, non-stress test and late decelerations in a patient at 41 weeks of gestation. Six hours after the last dose these changes gradually disappeared. Bitolterol is one of the more recent β2- adrenergic agonists. It is a prodrug which, when inhaled, is activated within the lung by esterase hydrolysis to the active compound, colterol. The effects and side effects of Tulobuterol, a fl2- adrenergic stimulant drug, have been reviewed. Side effects reported in the studies are similar in type, incidence, and severity to those reported for other drugs within this group, the most common being tremor and palpitations. Other side effects include headache, dizziness, vertigo, heartburn, jitteriness, and nervousness. Ibopamine is a another orally active dopamine derivative that has been studied in patients with congestive heart failure.

SYNOPSIS We have studied the effect of isometheptene, an indirectly acting sympathomimetic with a reported anti-migraine action, on carotid blood flow and the distribution of carotid blood flow throughout the cephalic circulation of the cat, using 15μm-microspheres. Microspheres measuring 15μm in diameter were used to separate capillary flow from flow through the arteriovenous anastomoses. Apart from decreasing carotid blood flow, isometheptene vigorously reduced the fraction of carotid blood flow shunted through the arteriovenous anastomoses. This mode of action of isometheptene may be relevant to its beneficial effect in migraine.

SYNOPSIS Forty female and 16 male adult migraineurs were subjects in a double-blind, three-way crossover trial to compare the effectiveness and safety of isometheptene mucate, acetaminophen, and dichloralphenazone combination (Midrin) with that of acetaminophen alone and of placebo. Forty-three patients had common migraine and 13 had classic migraine. Each subject and the investigator evaluated the effectiveness of medication in 6 headache episodes (two replications of each test medication); subjects also rated peak headache severity for each of the six episodes. For subjects' evaluations of relief and headache severity and investigator's assessments of relief, the isometheptene combination proved superior (P

We have studied the effect of isometheptene, an indirectly acting sympathomimetic with analgesic and antispastic properties, on secretin-cholecystokinin-stimulated pancreatic and biliary outputs. Isometheptene, infused intravenously at a dose of 100 mg in 30 min, significantly inhibited bicarbonate, enzyme, and bilirubin output in eight healthy subjects (compared to control values, the maximum percent inhibition was 34% for bicarbonate, 57% for lipase, 61% for chymotrypsin, and 86% for bilirubin). In four cholecystectomized subjects, the drug inhibited only pancreatic outputs. The inhibitory effect on pancreatic secretion, coupled with the analgesic action, suggest a potential benefit of this drug in acute pancreatic pathology.

The classification, biochemistry, precipitating factors, differential diagnosis, treatment of acute attacks, and prophylactic therapy of migraine headaches are reviewed. The biochemistry of both classic (prodromal symptoms) and common (no prodromal symptoms) migraines is poorly understood, but appears to involve serotonin. Although their clinical importance is not clear, common precipitating factors include coffee, tea, and cola beverages; chocolate, cheese, and alcohol; light stimulation, stress, fasting, lack of sleep, and fever; and reduced estrogen levels. The symptomatic treatment of acute attacks with ergot preparations, isometheptene, flufenamic acid, analgesics and sedatives is reviewed. Prophylactic therapy with methysergide maleate, tricyclic compounds, monoamine oxidase inhibitors, propranolol, and 5-hydroxytryptophan is also discussed.

trans-(E)-2-Methyl-6-methylamino-2-hepten-1-ol (6) and cis-(Z)-2-methyl-6-methylamino-2-hepten-1-ol (13), two in vivo metabolites from the antispasmodic agent isometheptene (2), ((±)–N,1,5-trimethyl-4-hexenylamine) have been synthesized. In the first synthesis of the trans isomer, the N-trifluoroacetyl derivative of 2 was oxidized with selenium dioxide in ethanol to give trans-2-methyl-6-N-methyltrifluoroacetamido-2-hepten-1-al (4). Aldehyde (4) was converted to 6 by reaction with sodium borohydride in ethanol. In the second synthesis, trans-2-methyl-6-oxo-2-hepten-1-ol ethylene ketal (8) and cis-2-methyl-6-oxo-2-hepten-1-ol ethylene ketal (11) were hydrolyzed without isomerization to hydroxyketones 9 and 12. Both 9 and 12 were reductively aminated to the desired metabolites, 6 and 13.

Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, alpha-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT(1B/1D) receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT(2) receptor antagonists, Ca(2+) channel blockers, and beta-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT(1-7)), adrenergic (alpha(1), alpha(2,) and beta), calcitonin gene-related peptide (CGRP(1) and CGRP(2)), adenosine (A(1), A(2), and A(3)), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon.

SYNOPSIS Regional cerebral blood flow (rCBF) and cerebral vasomotor responses to 5% CO2 inhalation were measured before and after pharmacologic μ- or β-adrenoceptor manipulation in Migraine (M) and Cluster headaches (C). Responses of 77 vascular headache patients (M =66 and C = 11) were compared to those of 15 Muscle contraction headache (MCH) and 64 normal volunteers. Oral drugs were: Peripheral μ-adrenoceptor stimulator:isometheptene (Midrin(r)), peripheral μ-blocker:dihydroergotoxin (Hydergine(r)), centrally acting μ-blocker:clonidine (Catapres(r)), peripheral β-blocker:propranolol (Inderal(r)), peripheral β-stimulator:isoproterenol (Isuprel(r)). Peripheral μ stimulation markedly reduced rCBF during headache but effect lessened after headache subsided in M and C. Peripheral μ-blockade and β-stimulation increased CBF in M and C. Peripheral β-blockade markedly decreased CBF during headache in M but caused only small CBF reductions when headache-free. Peripheral adrenoceptor effects on rCBF in M and C were greatest on most recent headache side. Central effects of clonidine were opposite (greatest on non-headache side). Excessive CO2 responses were greatest on side of headache. After peripheral μ-stimulation, peripheral μ-blockade, peripheral β-stimulation or blockade, CO2 responses were restored toward normal but not after central μ-blockade. In MCH. contrary to M and C, μ-stimulation had no effect on CBF or CO2 responses. There appears to be an asymmetrical adrenoceptor disorder in M and C possibly due to sympathetic denervation-hypersensitivity.

A rapid GLC assay for acetaminophen, dichloralantipyrine, and isometheptene mucate in capsules was developed. These substances are chromatographed directly, using phenyl methyl silicone gum as the stationary phase. The standard calibration curves are linear up to 14 mg/ml, with a lower limit of sensitivity of 2 mg/ml. This method is simple and rapid and does not require derivative formation.

trans-(E)-2-Methyl-6-methylamino-2-hepten-1-ol (6) and cis-(Z)-2-methyl-6-methylamino-2-hepten-1-ol (13), two in vivo metabolites from the antispasmodic agent isometheptene (2), ((±)–N,1,5-trimethy...