A new association of molecules able

to STOP THE MIGRAINE AURA and

PREVENT MIGRAINE through central
neuromodulation and peripheral
desensitisation.

www.aurastop.it
 migraine
Among the many forms of headache, MIGRAINE is the most common
and disabling. It affects almost 10 million people in Italy in episodic form,
but for more than 7 million patients, it becomes more frequent, then
persistent and, therefore, chronic.
Numerous epidemiological studies show that migraine
affects approximately 15-18% of women and 6%
of men in their lifetime, with a peak prevalence in the
period of increased productivity, between 25 and 55 years.
The disabling character of headache makes it a social
disease(1-2).
The WHO has included migraine among the 10 most disabling
diseases. About 1/5 of patients with migraine suffer migraine with
aura accounting for more than 1 million people in Italy.
migraine with aura
VISUAL AURA
The typical aura is represented by visual symptoms. Gradual
development, duration no longer than one hour, the presence
of positive and negative symptoms and complete reversibility
are the characteristics that identify the aura. The visual variant
is the most common type of aura and usually occurs in the form
of fortification spectra, with star-shaped figures initially near the
point of fixation and which gradually spread to the right or to
the left, assuming a convex shape with laterally angled glittering
edges leaving absolute or relative scotomas. In other cases
there is a blind spot progressing gradually without positive
phenomena.
SOMATOSENSORY AURA
Visual aura is sometimes followed by sensory disturbances
mostly like “stings of pins”, which slowly spread from the end of
a limb up to affect unilaterally an area of the face.
N COMPLEX AURA
A
d
E
s Less frequently speech disorders, mostly represented by
g H
r
B Q
L
aphasia, ie by difficulty expressing thoughts or simple words,
m
i
F
N
occur after sensory disturbances.
p
c
Symptoms usually appear one after the other: visual disturbances
occur first, followed by somatosensory symptoms and aphasia, but
the order of appearance can also be inverse or follow a different
sequence. A migraine crisis similar to that of which the patients have
regular experience almost always follows; sometimes the aura is not
followed by pain.
 factors influencing migraine the components of aurastop
AURASTOP is indicated for the treatment of migraine aura and
prevention of migraine without aura, because of a new association of
molecules.

BASED OK
Four non-mutually excluding mechanisms are implicated in the
pathophysiology of MIGRAINE:

A. the peripheral sensitization of the trigeminal-vascular system;

B. the sensitization of the caudal trigeminal nucleus and other structures

of the nociceptive system of the central nervous system (CNS), a
process in which CGRP (calcitonin gene-related peptide) plays a major
role.
5-HTP Mg++ PARTHENIUM

C. the activation of the “migraine generator” in the brainstem by

glutamate

D. the cortical spreading depression underpinning the phenomenon of

migraine aura.

By combining the action of the three components 5-HTP, MG and

PARTHENIUM, AuraStop is able to achieve a synergistic effect by
acting on the 4 above mentioned mechanisms in migraine prevention
and reduction or rapid disappearance of the aura phenomenon,
when taken at its beginning.
 how components of aurastop AFFECT MIGRAINE AURA

Excitatory action of glutamate (A) (C)

ANTAGONIZED BY THE ACTION OF 5-HTP TRP receptor activation resulting in

the release of CGRP (B)
The 5-HTP extracted from the seeds of
Griffonia simplicifolia is metabolized by ANTAGONIZED BY THE ACTION OF
specific enzymes in kynurenic acid (3), the TANACETUM PARTHENIUM
active compound in the kynurenic pathway Tanacetum Parthenium is a perennial
which antagonizes the excitatory action of herbaceous plant, a member of the
the gutamatergic acid (4) also at the central composite family, which, through its
level, being able to pass the blood-brain main active component, parthenolide,
barrier, through the blockade of the NMDA interacts with the processes involved in
receptor that is in fact overactive during a the development of the aura. The agents
migraine attack. likely to cause migraine are activators of
TRP receptors that, through the release
of CGRP from perivascular terminals of
5-HTP sensory neurons, contribute to neurogenic
inflammation leading to painful attacks. This
cascade of events can be blocked by
parthenolide, one of the antagonists
of TRP receptors (9) (10).

PARTHENIUM

Cortical Spreading Depression (D)

PROGRESSION INHIBITED BY MG
Magnesium deficiency can induce cortical spreading
depression (5) (6) (7), and then result in the aura
phenomenon. Mg inhibits NMDA receptor mainly
involved in the glutamatergic excitatory activity
leading to neurogenic inflammation and, at the central
level, to the aura phenomenon (8)

Mg++
 how aurastop components act
EFFECT OF 5-HTP
Glutamate is the main excitatory neurotransmitter
in both I° and II° order neurons: it is in fact known
to be involved in the activation of the trigeminal-
vascular system (A) and in the “migraine
generator” (C) in the brainstem and then in the
migraine attack. NMDA (N-methyl-D-Aspartate)
is a postsynaptic ionotropic receptor (Figure
1) which is involved in peripheral and central
glutamatergic sensitization.
IN MIGRAINE PREVENTION
Glutamate level is regulated by
the Kynurenine pathway (Figure 2)
that, in normal condition transforms
L-Tryptophan in neuroactive
metabolites, such as the Kynurenic
acid (Kyna), through the kynurenine
aminotransferase II. This stops the
release of glutamate and glutamatergic
neurotransmission by blocking the
binding site with glycine Glu N1 and
quinolinic acid (QUINA) a neurotoxic
Glu N2 agonist.
Fig 2: Kynurenine pathway
Kynurenic acid, derivated from the metabolism of L-Tryptophan, is an
endogenous antagonist of NMDA receptors whose concentration in
the brain can be increased as a result of systemic administration of its
precursor 5-HTP (11) (12) (13) (24).
EFFECT OF MG++
Intracellular magnesium at concentration within the normal range acts
as a physiological calcium-channel blocker limiting the “toxic” effects
of excessive intracellular levels of calcium, while low concentrations of
magnesium favors the formation of free radicals and, consequently, toxic
concentrations of NO radicals that are trigger mechanisms for migraine
attacks (14).
Fig 1: Representation of the
NMDA receptor.
Numerous studies have consistently observed low levels of
magnesium in migraine patients (15). Magnesium deficiency in fact
may cause dysfunction of serotonin receptors and affect the synthesis
and release of several neurotransmitters including the glutamatergic
neurotransmitters (NMDA) leading to neurogenic inflammation and
central and peripheral sensitization.
 mode of use
EFFECT OF TANACETUM PARTHENIUM

Parthenolide is a potent inhibitor of NOS

expression and the consequent synthesis of nitric
oxide (NO), which together with the CGRP and MODE OF USE IN ADULTS
substance P, is the principal pro-inflammatory
In the treatment of MIGRAINE AURA
neuro-peptide of the nociceptive terminals (16). Partenolide Mode of use: 1 tablet at the beginning of the aura followed by a 2nd
tablet at the onset of pain.
Parthenolide is an antagonist of TRPA1 receptor, mainly distributed on
dorsal root ganglia and trigeminal ganglia nociceptors, whose activation
causes a number of local proinflammatory responses, due to the release of In the prevention of MIGRAINE WITHOUT AURA
proinflammatory neuropeptides. This is called “neurogenic inflammation”, Mode of use: 1 tablet 2 times daily for 3 months
a crucial process of migraine pathophysiology

The agents causing migraines are activators of TRP receptors. The latter, In the treatment of MENSTRUAL MIGRAINE
through the release of CGRP from perivascular terminals of sensory Mode of use: 1 tablet 2 times daily from the 2nd day before
neurons, cause the neurogenic inflammation leading to the painful crisis. menstruation to the end of menstruation
Such a cascade of events can be blocked by Parthenolide, an antagonist
of TRP receptors.
In the treatment of MIGRAINE attack
Widely used for many years in Western Countries for the prevention of Mode of use: 2 tablets together
migraine (with the name of feverfew) (17) (18) and mentioned in the American,
Canadian (19) and Italian (20) Guidelines on the prevention of migraine, the
beneficial effects of Parthenolide have been recently emphasized by
several studies which confirmed its efficacy in migraine prevention, through PEDIATRIC USE
a reduction of both frequency and severity of attacks (21) (22) (23) (24). The
same studies also highlighted that its analgesic activity could also be of In the prevention of MIGRAINE and TENSION-TYPE HEADACHE
use at the onset of migraine attack. Mode of use: 1 sachet 2 times daily for 2-3 months.

In the treatment of MIGRAINE AURA

Mode of use: 1 sachet at the beginning of aura

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of healthcare for patients with migraine in five European countries: results fromthe International Burden of Migraine Study (IBMS) J Headache Pain.2012;13:361–78.
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6. Charles AC, Baca SM. Cortical spreading depression and migraine. Nat Rev Neurol. 2013;9:637–44.
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induced by magnesium deficiency in rats. Br J Pharmacol. 2001 Nov; 134(6):1227-36.
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in rat. Exp Neurol. 2012 Aug;236(2):2017-14.
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attacks. Neurosciences (Riyadh) 2011 Oct;16(4):320-3
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 Available in packs of 20 tablets or 14 sachets.

AVERAGE CONTENT PER SERVING PER SERVING

(1 tablet) (2 tablets)
MAGNESIUM 185 mg 370 mg
Tanacetum parthenium 150 mg 300 mg
of which parthenolide 1200 µg 2400 µg
100 mg 200 mg
Griffonia simplicifolia of which 5-htp
20 mg 40 mg

AVERAGE CONTENT PER SERVING PER SERVING

(1 sachet) (2 sachets)
250 mg 500 mg
for the exclusive use material of health professionals

Griffonia simplicifolia of which 5-htp

50 mg 100 mg
MAGNESIUM 100 mg 200 mg
Tanacetum parthenium of which 75 mg 150 mg
parthenolide 600 µg 1200 µg

www.aurastop.it
edition: January 2017