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Nocturnal plasma melatonin profile and melatonin
kinetics during infusion in status migrainosus
Claustrat B.; Brun J.; Geoffriau M.; Zaidan R.; Mallo C.;
Chazot G.
B. Claustrat, Serv. Radiopharmacie/Radioanalyse, Hopital
Neurologique, 59 Boulevard Pinel, 69003 Lyon France
Cephalalgia (Norway), 1997, 17/4 (511-517)
The plasma melatonin profile was significantly disturbed
(phase-shift of the maximum melatonin level) in four out of
six female sufferers from status migrainosus, compared with
nine healthy controls. The number of secretion peaks was
similar in both groups. A nocturnal 20 pg melatonin infusion
(from 21.00 to 01.00 h) evoked plasma melatonin levels
slightly higher than a physiological secretion peak. During
infusion, the episodes of secretion were reinforced and the
endogenous plasma profile was phase-advanced in two patients
displaying a phase-delay. These data suggest impaired pineal
function in migraine. In the absence of side effects of
melatonin infusion, the relief of certain migraine symptoms
described by our patients might support a controlled trial of
melatonin in migraine.
Pharmacology of serotonin as related to
anesthesia
Gyermek L.
Department of Anesthesiology, Harbor-UCLA Medical Center,
1000 West Carson Street, Torrance, CA 90509 USA
Journal of Clinical Anesthesia (USA), 1996, 8/5
(402-425)
Serotonin (5-hydroxytryptamine) is an important biogenic
amine that fulfills the role of neurotransmitter and
neuromodulator. It has been a focus of interest during the
last decade. Its diversity of pharmacologic actions is related
to a wide variety of receptors and effector mechanisms. Serum
serotonin receptor families have been identified thus far.
They are genetically different transmembrane proteins composed
of several hundred amino acids. The majority of these are
G-protein-coupled, except the 5-HT3 receptors, which are
directly ligand gated to fast ion channels. Serotonin is
widely distributed in the body within the central and
peripheral nervous systems, smooth muscles, and platelets, in
particular. Consequently, its effects manifest mainly in these
organs and influence a wide variety of neural, vascular,
smooth muscle, and platelet functions. (Melatonin, a
physiologically active metabolite of serotonin, is also
instrumental in affecting many neural and hormonal functions.)
Several selective agonists and particularly many selective
antagonists have been developed for serotonin, which helped
the serotonin receptor subtype classification. Some of these
drugs are also used therapeutically in the treatment of
migraine (eg, sumatriptan, which is a 5-HT1 receptor agonist),
vascular disorders (5-HT2 antagonists), and nausea and
vomiting (5-HT3 antagonists, eg, dolasetron, granisetron,
ondansetron, and tropisetron), and have been investigated in
gastrointestinal motility disorders (5-HT4 antagonists) and
behavioral psychopathologies (5-HT1 agonists and 5-HT2-4
antagonists). Serotonin reuptake inhibitors are of particular
clinical importance in the treatment of psychological
illnesses. Future use of these drugs is also envisioned in the
treatment of certain types of pain syndromes. Awareness of the
serotonergic drugs and the recognition of possible drug
interactions among drugs that influence serotonergic
mechanisms in humans are becoming increasingly important in
the practice of anesthesiology.
Pathogenesis of posttraumatic headache and
migraine: a common headache pathway?
Packard RC; Ham LP
Headache Management and Neurology, Pensacola, FL 32503,
USA.
Headache (United States) Mar 1997, 37 (3)
p142-52
In recent years, research implicating biochemical
abnormalities in various pathological conditions has
spiralled. Headache is an area in which numerous research
studies have been conducted examining biochemical alterations.
We have noticed several similarities in biochemical changes
reported to occur in migraine and in experimental traumatic
brain injury. The most common symptom in mild head injury or
mild traumatic brain injury is headache which, in many
instances, resembles migraine but has a poorly understood
pathophysiology. Biochemical mechanisms believed to be similar
in both conditions include: increased extracellular potassium
and intracellular sodium, calcium, and chloride; excessive
release of excitatory amino acids; alterations in serotonin;
abnormalities in catecholamines and endogenous opioids;
decline in magnesium levels and increase in intracellular
calcium; impaired glucose utilization; abnormalities in nitric
oxide formation and function; and alterations in
neuropeptides. In this paper, these proposed biochemical
alterations will be reviewed and compared. Very similar
alterations suggest posttraumatic headache associated with
mild head injury and migraine may share a common headache
pathway. (114 Refs.)
[Migraine--diagnosis, differential diagnosis and
therapy]
Diener HC
Klinik und Poliklinik fur Neurologie, Universitat
Essen.
Ther Umsch (Switzerland) Feb 1997, 54 (2) p64-70
Migraine is caused by intermittent brain dysfunction.
Attacks result in severe unilateral headache with nausea,
vomiting, photophobia, phonophobia and general weakness. The
prevalence of migraine is 12 to 20% in women and 8 to 12% in
man. Treatment of an acute attack is done by antiemetics in
combination with analgesics. Severe migraine attacks are
treated with ergotamine or sumatriptan. Parenteral treatment
is performed most efficiently and safely with i.v. ASA.
Frequent and severe attacks require prophylaxis. Drugs of
first choice are metoprolol, propranolol, flunarizine and
cyclandelate. Substances of second choice are valproic acid,
DHE, pizotifen, methysergide and magnesium. Homeopathic
remedies are not superior to placebo. Nonpharmacological
treatment consists of sport therapy and muscle relaxation
techniques.
Magnesium taurate and fish oil for prevention of
migraine.
McCarty MF
Nutrition 21, San Diego, CA 92109, USA.
Med Hypotheses (England) Dec 1996, 47 (6) p461-6
Although the pathogenesis of migraine is still poorly
understood, various clinical investigations, as well as
consideration of the characteristic activities of the wide
range of drugs known to reduce migraine incidence, suggest
that such phenomena as neuronal hyperexcitation, cortical
spreading depression, vasospasm, platelet activation and
sympathetic hyperactivity often play a part in this syndrome.
Increased tissue levels of taurine, as well as increased
extracellular magnesium, could be expected to dampen neuronal
hyperexcitation, counteract vasospasm, increase tolerance to
focal hypoxia and stabilize platelets; taurine may also lessen
sympathetic outflow. Thus it is reasonable to speculate that
supplemental magnesium taurate will have preventive value in
the treatment of migraine. Fish oil, owing to its
platelet-stabilizing and antivasospastic actions, may also be
useful in this regard, as suggested by a few clinical reports.
Although many drugs have value for migraine prophylaxis, the
two nutritional measures suggested here may have particular
merit owing to the versatility of their actions, their safety
and lack of side-effects and their long-term favorable impact
on vascular health. (94 Refs.)
Prophylaxis of migraine with oral magnesium:
results from a prospective, multi-center, placebo-controlled
and double-blind randomized study.
Peikert A; Wilimzig C; Kohne-Volland R
Department of Neurology and Clinical Neurophysiology,
Munich-Harlaching Clinic, Germany.
Cephalalgia (Norway) Jun 1996, 16 (4) p257-63
In order to evaluate the prophylactic effect of oral
magnesium, 81 patients aged 18-65 years with migraine
according to the International Headache Society (IHS) criteria
(mean attack frequency 3.6 per month) were examined. After a
prospective baseline period of 4 weeks they received oral 600
mg (24 mmol) magnesium (trimagnesium dicitrate) daily for 12
weeks or placebo. In weeks 9-12 the attack frequency was
reduced by 41.6% in the magnesium group and by 15.8% in the
placebo group compared to the baseline (p < 0.05). The
number of days with migraine and the drug consumption for
symptomatic treatment per patient also decreased significantly
in the magnesium group. Duration and intensity of the attacks
and the drug consumption per attack also tended to decrease
compared to placebo but failed to be significant. Adverse
events were diarrhea (18.6%) and gastric irritation (4.7%).
High-dose oral magnesium appears to be effective in migraine
prophylaxis.
Electromyographical ischemic test and intracellular
and extracellular magnesium concentration in migraine and
tension-type headache patients.
Mazzotta G; Sarchielli P; Alberti A; Gallai V
Interuniversity (Perugia-Rome-Sassari-Bari) Centre for the
Study of Headache and Neurotransmitter Disorders of the CNS,
Italy.
Headache (United States) Jun 1996, 36 (6)
p357-61
Headache has often been described in the hyperexcitability
syndrome which recognizes an alteration of calcium and
magnesium status in its etiopathogenesis. Moreover, in
migraine patients magnesium has been shown to play an
important role as a regulator of neuronal excitability and,
therefore hypothetically, of headache. The present research
involves a neurophysiological evaluation and magnesium status
assessment of a group of headache patients. Nineteen patients
(15 women and 4 men) with episodic tension-type headache and
30 patients (27 women and 3 men) with migraine without aura
were examined. An ischemic test was carried out on the right
arm with electromyographic (EMG) recording of motor unit
potential activity during the interictal period. The
determination of extracellular (serum and saliva) and
intracellular (red and mononuclear blood cells) magnesium was
also performed. The EMG test was positive in 25 of 30 migraine
patients and in 2 of 19 tension-type headache patients.
Between the two patient groups, there were no significant
variations in the concentration of extracellular and white
blood cell magnesium, while the red blood cell concentration
of this mineral in the group of migraineurs was significantly
reduced with respect to that in the group of tension-type
headache patients (P < 0.05). The positive EMG test was
significantly associated with a low concentration of red blood
cell magnesium (P < 0.0001). These results confirm previous
findings by demonstrating different etiopathogenic mechanisms
as the basis of migraine and tension-type headache. Migraine
seems to be related to an altered magnesium status, which
manifests itself by a neuromuscular hyperexcitability and a
reduced concentration in red blood cells.
Efficacy and tolerability of subcutaneous
sumatriptan administered using the IMITREX STATdose
System.
Mushet GR; Cady RK; Baker CC; Clements B; Gutterman DL; Davis
R
Georgia Headache Treatment Center, Augusta, USA.
Clin Ther (United States) Jul-Aug 1996, 18 (4)
p687-99
The efficacy and tolerability of subcutaneous (SC)
sumatriptan administered with the IMITREX (sumatriptan
succinate) STATdose System, which circumvents the need for
patients or health care professionals to handle a syringe,
were evaluated in two randomized, double-masked,
parallel-group, placebo-controlled, multicenter studies. In
the clinic, 158 adults with migraine diagnosed according to
International Headache Society criteria received SC
sumatriptan (6 mg) or placebo delivered with the IMITREX
STATdose System for treatment of a migraine attack. By 120
minutes after SC dosing, 73% and 79% of sumatriptan-treated
patients, compared with 28% and 37% of placebo-treated
patients in studies 1 and 2, respectively, experienced
headache relief (a statistically significant difference).
Clinical disability scores 120 minutes after dosing showed
that 75% and 85% of sumatriptan-treated patients, compared
with 30% and 42% of placebo-treated patients, were normal or
only mildly impaired (a statistically significant difference).
Similar efficacy rates were observed for nausea, phonophobia,
and photophobia. No serious or unusual adverse events
occurred, and no clinically relevant abnormalities in
laboratory test values were reported. Based on these results,
we concluded that SC sumatriptan (6 mg) administered using the
IMITREX STATdose System is effective for the treatment of
migraine. The efficacy and tolerability profiles of SC
sumatriptan administered with this device are similar to those
reported for SC sumatriptan administered with a conventional
syringe.
A double-blind study of subcutaneous
dihydroergotamine vs subcutaneous sumatriptan in the treatment
of acute migraine.
Winner P; Ricalde O; Le Force B; Saper J; Margul B
Palm Beach Headache Center, Fla, USA.
Arch Neurol (United States) Feb 1996, 53 (2)
p180-4
OBJECTIVE: To assess the efficacy and tolerability of
subcutaneous dihydroergotamine mesylate (DHE-45) vs
subcutaneous sumatriptan succinate (Imitrex) for the treatment
of acute migraine with or without aura.
DESIGN: Double-blind, randomized trial with parallel
treatment arms.
SETTING: Clinics and private neurology practices.
SUBJECTS: Patients of either sex, with migraine with or
without aura, between the ages of 18 and 65 years.
INTERVENTIONS: Patients with moderate or severe head pain
were randomized to receive either 1 mg of subcutaneous
dihydroergotamine mesylate or 6 mg of subcutaneous sumatriptan
succinate. Patients rated head pain, functional ability,
nausea, and vomiting at baseline and at 0.5, 1, 2, 4, and 24
hours after the injection. Presence or absence of headache at
3 hours was calculated from collected data. If pain persisted
after 2 hours, a second injection of the same study medication
was allowed, and self-ratings were repeated 30 and 60 minutes
later. Follow-up data were collected at 24 hours.
MAIN OUTCOME MEASURES: Relief of head pain and recurrence
of successfully treated headache.
RESULTS: There were 295 evaluable patients. At 2 hours,
73.1% of the patients treated with dihydroergotamine and 85.3%
of those treated with sumatriptan had relief (P = .002). There
was no statistical difference in headache relief between the
groups at 3 or 4 hours. Headache relief was achieved by 85.5%
of those treated with dihydroergotamine and by 83.3% of those
treated with sumatriptan by 4 hours. By 24 hours 89.7% of
dihydroergotamine-treated patients and 76.7% of
sumatriptan-treated patients had relief (P = .004). Headache
recurred within 24 hours after treatment in 45% of the
sumatriptan-treated patients and in 17.7% of the
dihydroergotamine-treated patients (P < or = .001).
CONCLUSIONS: Both sumatriptan and dihydroergotamine were
effective in aborting migraine headaches. Headache recurrence
was two and a half time as likely with sumatriptan as with
dihydroergotamine.
Herbal products begin to attract the attention of
brand-name drug companies.
Cottrell K
Can Med Assoc J (Canada) Jul 15 1996, 155 (2)
p216-9
Many Canadians are interested in alternative medicine, and
burgeoning public interest in herbal remedies has not gone
unnoticed by Canada's drug companies. McNeil Consumer Products
recently began selling a migraine prophylaxis made from the
plant feverfew. Physicians who would like to see herbal
medications subjected to outcome studies and quality-control
standards, with evidence of risks and benefits being made
available to consumers, welcome the interest the companies are
showing. Meanwhile, physicians and pharmacists are trying to
respond to consumer demand by increasing their own knowledge
about herbal medications.
Long-time efficacy of cyclandelate and propranolol
in prophylaxis of migraine following four months of
treatment
Schellenberg R.; Schwarz A.; Niederberger U.; Bolsche F.;
Schindler M.; Gerber W.-D.; Wedekind W.; Soyka D.
Dr. R. Schellenberg, Talstrasse 29, D-35625 Huttenberg
Germany
Nervenheilkunde (Germany), 1997, 16/3 (183-187)
After a 4 months randomized double-blind study with
cyclandelate versus propranolol all patients kept a
miniaturized headache diary for one more year. Both duration
of migraine attacks in hours and the number of additional
analgetic medication were recorded monthly. Reduction of the
duration of migraine attacks in the clinical responders of the
cyclandelate treated patients remained nearly unchanged. In
the propranolol responders the duration of migraine attacks in
hours increased from the third month after finishing the
medication and reached values comparable to those at the
beginning of the active treatment. Intake of additional
analgetic medication during the 1-year-follow-up was lower in
the cyclandelate responders than in the
propranolol-responders. Cyclandelate can be described as an
effective long-lasting drug in migraine prophylaxis.
Sumatriptan use in a large group-model health
maintenance organization
Greiner D.L.; Addy S.N.
Kaiser Permanente, Box 6182, 2101 East Jefferson Street,
Rockville, MD 20849-6182 USA
American Journal of Health-System Pharmacy (USA), 1996, 53/6
(633-638)
The outcomes of sumatriptan use at a health maintenance
organization (HMO) were studied. The study was conducted
during one year beginning immediately after sumatriptan was
added to the formulary of a large group-model HMO. Subjects
were included on the basis of drug-use evaluation criteria, a
positive response to the first dose of sumatriptan
(administered at the HMO by a nurse), and ability to
participate in a telephone survey. Responders to the first
dose were eligible to receive up to six doses of sumatriptan
for home use. The telephone survey was designed to assess
sumatriptan's effects on migraine headache and to capture data
on quality of life, perceived problems with sumatriptan, and
patient satisfaction. Patients who received sumatriptan
between April and September 1993 were interviewed in late
September 1993; patients who received sumatriptan between
September and April 1994 were interviewed in late April 1994.
Of 180 patients surveyed, 160 (89%) had evaluable responses.
Migraine headache improved in two thirds of the patients.
Sumatriptan was more effective than previously used agents in
three fourths. The mean number of migraine headaches per
patient per month decreased from 7.4 to 4.2. Quality-of-life
indicators, such as time spent with friends, improved in three
fourths. Eighty-three percent reported missing fewer days from
work. Ninety percent said they would continue to take the
drug, despite a 44% incidence of drug-related problems. There
were no unexpected problems. A retrospective review showed
that utilization of the HMO's resources was reduced with
sumatriptan. Placing sumatriptan on an HMO's formulary led to
favorable effects on the frequency and severity of migraine
headache, patient quality-of-life indicators and productivity,
and resource utilization by the organization.
The effect of sumatriptan on brain monoamines in
rats
Mitsikostas D.D.; Papadopoulou-Daifotis Z.; Sfikakis A.;
Varonos D.
Department of Neurology, Athens Naval Hospital, 70
Dinokratous Street, Athens 115 21 Greece
Headache (USA), 1996, 36/1 (29-31)
Clinical data suggests that sumatriptan is effective in the
acute treatment of migraine. The vascular effects of the drug
have been invoked to explain this antimigraine efficacy.
However, the effect of sumatriptan on brain monoamines has not
previously been investigated. In order to study these
hypothetical effects, we administered the drug to 24 male
rats, subcutaneously, at three doses (0.3, 0.6, and 0.9 mg/kg
of body weight), and 30 minutes later, all animals were
decapitated. Dopamine, serotonin, and their metabolites 3,4
dihydroxyphenylacetic acid, 5-hydroxyindoleacetic acid, and
homovanillic acid concentrations were measured in the frontal
cortex, hypothalamus, striatum, and hippocampus, by high
performance liquid chromatography. Plasma concentrations of
the drug were also determined. The control group was treated
with NaCl 0.9%, given subcutaneously. Sumatriptan, at the dose
of 0.3 mg/kg did not alter the brain monoamine concentrations;
however, at the dose of 0.6 mg/kg, sumatriptan decreased
serotonin concentration in the hypothalamus and increased the
turnover of dopamine and serotonin in the hypothalamus and
striatum, while at the dose of 0.9 mg/kg, it augmented only
the turnover of serotonin in the hypothalamus. No dose-
dependent effect of the drug was found. This subcortical
antidopaminergic end antiserotoninergic effect of sumatriptan
may be involved in its antimigraine action.
In vivo administration of propranolol decreases
exaggerated amounts of serum TNF-alpha in patients with
migraine without aura. Possible mechanism of action.
Covelli V; Munno I; Pellegrino NM; Marinaro MR; Gesario A;
Massari F; Savastano S; Jirillo E
Acta Neurol (Napoli); 14(4-6):313-9 1992
Patients with migraine without aura (MWA) display elevated
amounts of Tumor Necrosis Factor (TNF)-alpha in their sera. In
this study in 18 patients with MWA the in vivo effect of
propranolol, a beta blocker agent, was evaluated with regard
to the TNF serum levels before and after treatment. Results
show that in 9 out 11 patients exaggerated serum
concentrations of TNF reverted to normality after three months
of therapy. Some hypotheses on the mechanisms of action of
propranolol in terms of modulation of the immune response are
formulated.
Concurrent use of antidepressants and propranolol:
case report and theoretical considerations
Nemeroff CB; Evans DL
Biol Psychiatry; 18(2):237-41 1983
The therapeutic indications for propranolol have been
steadily increasing in recent years. Propranolol and other
beta-adrenergic blocking agents are now generally acknowledged
to be helpful in the management of hypertension, certain
cardiac arrhythmias, migraine, essential tremor, angina
pectoris, and most recently, immediately after myocardial
infarction (Frishman, 1981; Norwegian Multicenter Study Group,
1982). Because of the myriad clinical settings in which
propranolol has been found to be of benefit, the interactions
of these drugs with other commonly utilized pharmacological
agents is of great pragmatic interest. In this report we
describe the successful concomitant clinical use of
propranolol and an antidepressant drug. This finding is also
of interest because of recent theories concerning the
mechanism of action of antidepressant drugs. Because
propranolol readily penetrates into the CNS, it blocks
beta-adrenergic receptors in both the periphery and the CNS
(Weiner, 1980). Much attention has been focused recently on
the effects of long-term antidepressant therapy on central
beta-adrenergic receptors in the brain as a possible mechanism
of action of these drugs. The concurrent use of propranolol
and an antidepressant drug in the patient described in this
report did not attenuate the therapeutic effects of the
antidepressant.
Nocturnal melatonin excretion is decreased in
patients with migraine without aura attacks associated with
menses
Brun J.; Claustrat B.; Saddier P.; Chazot G.
Cephalalgia (Norway), 1995, 15/2 (136-139)
Nocturnal melatonin excretion was studied throughout a
complete menstrual cycle in 10 women with migraine without
aura attacks associated with menses and 9 women controls.
Urine melatonin was determined by radioimmunoassay. The mean
nocturnal melatonin excretion throughout the cycle was
significantly lower in the migraine patients than in controls.
In the control group, melatonin excretion increased
significantly from the follicular to the luteal phase, whereas
no difference was observed in the migraine group. Results are
discussed in view of the role of the pineal gland in the
organization of biological rhythms and homeostasis in relation
to environmental conditions.
Urinary melatonin excretion throughoutthe ovarian
cycle in menstrually related migraine
Murialdo G.; Fonzi S.; Costelli P.; Solinas G.P.; Parodi C.;
Marabini S.; Fanciullacci M.; Polleri A.
Endocrinological/Metabol. Sci. Dept., Viale Benedetto XV, 6,
I-16132 Genoa Italy
Cephalalgia 1994 Jun;14(3):205-9
Nocturnal urinary melatonin excretion was significantly
decreased throughout an ovarian cycle in 12 migraine without
aura patients compared to 8 healthy controls. Normal increases
in urinary melatonin excretion during the luteal phase was
less pronounced in the migraine patients. Melatonin excretion
was further decreased during headache. The data indicate
impaired pineal function in migraine.
Nocturnal plasma melatonin levels in migraine: A
preliminary report
Claustrat B, Loisy C, Brun J, Beorchia S, Arnaud JL, Chazot
G
Headache (United States) Apr 1989, 29 (4) p242-5
We determined by radioimmunoassay plasma melatonin levels
on blood samples drawn at 11 p.m. in migraine patients and
control subjects. Ninety-three cephalalgic outpatients (75
females, 18 males) were compared to a control group (24
females, 22 males) matched according to age. Patients were
divided into subgroups presenting common migraine (n = 38);
ophthalmic migraine (n = 12); and tension headache associated
with ophthalmic or common migraine (n = 24), and associated
depressive status (n = 19). Statistical analysis revealed a
decrease in plasma melatonin levels for the entire migraine
population, compared to the control one, and a heterogeneity
in both controls and patients; this heterogeneity was found
mainly in the depressive and tension headache subgroups. When
the migraine population - from which the depressive patients
were excluded - was divided into male and female subgroups, a
decrease in plasma melatonin levels was observed only for the
female subgroups. Results are discussed with reference to the
role of the pineal gland in the synchronization of the
organism with the environmental conditions.
Octopamine and some related noncatecholic amines in
invertebrate nervous systems
Robertson H.A.; Juorio A.V.
Int. Rev. Neurobiol. (USA), 1976, Vol.19
(173-224)
In addition to the major monoamines (dopamine,
noradrenaline, serotonin) there exists in the nervous tissue
of all species examined a group of monoamines described as
exotic amines, trace amines or microamines. Among the
endogeneous microamines found in the mammalian brain are beta
phenylethylamine, phenylethanolamine, m and p tyramine,
octopamine and tryptamine. Despite their very low
concentrations, microamines are interesting for several
reasons: they are heterogeneously distributed within the
brain; they are present in the same subcellular fraction as
catecholamines and 5 HT; they have a high turnover rate; they
release and/or replace catecholamines from storage sites and
block reuptake; they may be excreted abnormally in the urine
of patients with migraine, Parkinson's disease, schizophrenia
and depression; some of them are behaviorally active.
Analytical procedures for micramines are described and their
biosynthesis and catabolism discussed. Out of them octopamine
proved to be the most prospective candidate as a transmitter
in the invertebrate nervous system as it fulfilled six of the
seven criteria for identification of chemical transmitters (it
has been shown to be present in neurons; presence of synthetic
enzymes as well as precursors and intermediates has been
demonstrated; it was released during nerve stimulation;
exogeneous octopamine mimics the effect of the released
transmitter; pharmacological agents interact with both the
synaptically released transmitter and octopamine in an
identical manner. The physiological means of inactivation
and/or removal from the synapse, however, remain unknown).
Among the other microamines, there is little evidence for a
role in invertebrates.
The co-occurrence of multiple sclerosis and
migraine headache: the serotoninergic link.
Sandyk R; Awerbuch GI
Int J Neurosci (England) Jun 1994, 76 (3-4)
p249-57
The occurrence of migraine headaches in patients with
multiple sclerosis (MS) has been recognized for quite some
time but the significance of this association to the
pathogenesis of MS largely has been ignored. Several reports
have documented that migraine headaches may occur during
exacerbation of symptoms and may even herald the onset of
relapse in MS. We present three MS patients in whom migraine
headaches developed during a period of relapse. As migraine
has been linked to changes in serotonin (5-HT) functions, the
emergence of migraine headaches coincident with the onset of
relapse implicates dysregulation of the 5-HT system in the
pathophysiology of MS. This hypothesis is plausible
considering the evidence that MS patients are serotonergically
depleted and that 5-HT is involved in maintaining the
integrity of the blood brain barrier, disruption of which is
believed to occur in the initial stages of exacerbation of MS
symptoms. Furthermore, this hypothesis may have potential
therapeutic implications in the treatment of exacerbations of
MS and possibly in the prevention of relapse in the
disease.
Urinary melatonin excretion throughout the ovarian
cycle in menstrually related migraine
Murialdo G; Fonzi S; Costelli P; Solinas GP; Parodi C;
Marabini S; Fanciullacci M; Polleri A
Cephalalgia (Norway) Jun 1994, 14 (3) p205-9
Nocturnal urinary melatonin excretion was significantly
decreased throughout an ovarian cycle in 12 migraine without
aura patients compared to 8 healthy controls. Normal increases
in urinary melatonin excretion during the luteal phase was
less pronounced in the migraine patients. Melatonin excretion
was further decreased during headache. The data indicate
impaired pineal function in migraine.
The influence of the pineal gland on migraine and
cluster headaches and effects of treatment with picoTesla
magnetic fields.
Sandyk R
Int J Neurosci (England) Nov-Dec 1992, 67 (1-4)
p145-71
For over half a century the generally accepted views on the
pathogenesis of migraine were based on the theories of Harold
Wolff implicating changes in cerebral vascular tone in the
development of migraine. Recent studies, which are based on
Leao's concept of spreading depression, favor primary neuronal
injury with secondary involvement of the cerebral circulation.
In contrast to migraine, the pathogenesis of cluster headache
(CH) remains entirely elusive. Both migraine and CH are
cyclical disorders which are characterised by spontaneous
exacerbations and remissions, seasonal variability of
symptoms, and a relationship to a variety of environmental
trigger factors. CH in particular has a strong circadian and
seasonal regularity. It is now well established that the
pineal gland is an adaptive organ which maintains and
regulates cerebral homeostasis by "fine tuning" biological
rhythms through the mediation of melatonin. Since migraine and
CH reflect abnormal adaptive responses to environmental
influences resulting in heightened neurovascular reactivity, I
propose that the pineal gland is a critical mediator in their
pathogenesis. This novel hypothesis provides a framework for
future research and development of new therapeutic modalities
for these chronic headache syndromes. The successful treatment
of a patient with an acute migraine attack with external
magnetic fields, which acutely inhibit melatonin secretion in
animals and humans, attests to the importance of the pineal
gland in the pathogenesis of migraine headache. (242
Refs.)
Is migraine due to a deficiency of pineal
melatonin?
Toglia JU
Ital J Neurol Sci (Italy) Jun 1986, 7 (3)
p319-23
Recent clinical observations favor the theory that migraine
is caused by a primary injury of cerebral neurons with
secondary involvement of intracranial and extracranial blood
vessels. The primary injury is attributed to disruption of
cerebral neurotransmitters and particularly the
neuroadrenergic and serotonergic systems. These theories have
not explained the importance of environmental factors, which
so frequently trigger migraine. The author suggests that the
pineal gland, which is outside the CNS unprotected by blood
brain barrier and sensitive to external stimuli, could act as
the intermediate causative factor of migraine, via a
derangement of melatonin. (47 Refs.)
Melatonin in humans physiological and clinical
studies.
Wetterberg L
J Neural Transm Suppl (Austria) 1978, (13)
p289-310
Studies are reported of the variation of melatonin in
serum, plasma urine and cerebrospinal fluid in normal subjects
and in patients with various diseases. The diurnal variation
of plasma and urine melatonin found in healthy controls on a
regular dark-sleep pattern persisted when the subjects slept
in light. The effect of sleep deprivation and of rapid light
exposure at night is reported. There was a correlation between
melatonin in morning urine and plasma at 2 a.m. Four hours of
extended darkness in the morning as well as a 9-hour shift of
sleep and activity cycles following travel affected the
melatonin rhythm. The night increase in plasma melatonin
preceeded both the cortisol and prolactin rise. A single oral
dose of 4.3 X 10(5) nmol of melatonin given to a 44-year-old
healthy male gave a peak plasma value of 624 nmol/l after 30
min. Plasma melatonin was not affected by electroconvulsive
therapy, TRH-injection, L-Dopa or bromoergocryptine orally.
Patients with alcoholism, migraine, postoperative pinealoma,
panhypopituitarism, hereditary dystonia and schizophrenics on
propranolol exhibited a decreased amplitude of their diurnal
rhythm of melatonin. Two patients with pituitary tumors had
occasional high levels of plasma melatonin. The change in
melatonin secretion in human is apparently controlled by a
mechanism which is at least party influenced by environmental
lighting conditions, drugs and different disease states. (27
refs.)
FEVERFEW (Tanacetum pathenium):
Feverfew appears to work in the treatment and prevention of
migraine headaches by inhibiting the release of blood vessel
dilating substances from platelets (serotonin and histamine),
inhibiting the production of inflammatory substances
(leukotrienes, serine proteases, etc.), and re-establishing
proper blood vessel tone. Commercial sources providing
assurance of botanical identity and minimum required level of
parthenolides are needed (Awang DVC. Feverfew. Car Pharm J
122:266-70, 1989).
In vitro Study: Feverfew was found to contain a factor that
inhibits prostaglandin synthesis, but differs from salicylates
by not inhibiting cyclo-oxygenase by prostaglandin (PG)
synthase. "The ability of feverfew to inhibit PG production
may account for its effectiveness as a herbal remedy in
conditions responding to acetylsalicylate and like-acting
drugs" (Collier HOJ, Butt NM, McDonald-Gibson WJ, Saeed SA.
Extract of feverfew inhibits prostaglandin biosynthesis.
Letter. lancet October 25, 1980).
The dosage of feverfew used in one double-blind study was
one capsule containing 25 mg of the freeze-dried pulverized
leaves twice daily; in another double-blind study it was one
capsule containing 82 mg of dried powdered leaves once daily.
While these low dosages may be effective in preventing an
attack, a higher dose (I to 2 grams) may be necessary during
an acute attack.
Note: The efficacy of feverfew is dependent upon adequate
levels of parthenolide, the active ingredient. (The
preparations used in successful clinical trials have a
parthenolide content of 0.4-0.66%.)
Animal Ex vivo Study: Extracts of fresh feverfew caused a
dose- and time dependent, irreversible inhibition of the
contractile response of rabbit aortic rings to all
receptor-acting agonists tested. The presence of potentially
SH reacting parthenolide and other sesquiterpene
alpha-methylenebutyrolactones in, these extracts, and the
close parallelism of pure parthenolide, suggest that the
inhibitory effects are due to these compounds. Extracts of the
dry leaves were not inhibitory and actually caused potent and
sustained contractions of aortic smooth muscle; these extracts
were found to be devoid or parthenolide or butyrolactones
(Barsby RWJ, Salan U, Knight BW, Hoult JRS. Feverfew and
vascular smooth muscle: Extracts from fresh and dried plants
show opposing pharmacological profiles, dependent upon
sesquiterpene lactone content. Planta Medica 59:20-5,
1993).
Chemical Analysis: The parthenolide content of over 35
different commercial preparations of feverfew was determined
by bioassay, 2 HPLC methods, and NMR. The results indicate a
wide variation in the amts. of parthenolide in commercial
preparations. The majority of products contained no
parthenolide or only traces (Heptinstall S et al. Parthenolide
content and bioactivity of feverfew (Tanacetum parthenium (L.)
Schultz-Bip.). Estimation of commercial and authenticated
feverfew products. J Pharm Pharmaco1 44:391-5, 1992).
WARNING: No long-term toxicity studies have been conducted.
While feverfew is extremely well-tolerated and no serious side
effects have ever been reported, chewing the leaves can result
in small ulcerations in the mouth and swelling of the lips and
tongue in about 10% of users (Awang DVC. Feverfew. Can Pharml
122:266-70, 1989).
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