334 Therapy of Selected Diseases
headaches but not in other forms of head-
‡ Migraine
Migraine is a syndrome characterized by re-
current attacks of intense headache and nau-
sea that occur at irregular intervals and last
for several hours. In classical migraine, the
attack is typically heralded by an “aura” ac-
companied by spreading homonymous vis-
ual field defects with colored sharp edges
(“fortification” spectra). In addition, the pa-
tient cannot focus on certain objects, has a
ravenous appetite for particular foods, and is
hypersensitive to odors (hyperosmia) or
light (photophobia). The exact cause of these
complaints is unknown; conceivably, the
underlying pathogenetic mechanisms in-
volve local release of proinflammatory me-
diators from nociceptive primary afferents
(neurogenic inflammation) or a disturbance
in cranial blood flow. In addition to an often
inherited predisposition, precipitating fac-
tors are required to provoke an attack, e. g.,
psychic stress, lack of sleep, certain foods.
Pharmacotherapy of migraine has two aims:
stopping the acute attack and preventing
subsequent ones.
Treatment of the attack. For symptomatic
relief, headaches are treated with analgesics
(acetaminophen, acetylsalicylic acid), and
nausea is treated with metoclopramide
(pp.116, 342) or domperidone. Since there
is delayed gastric emptying during the at-
tack, drug absorption can be markedly re-
tarded and hence effective plasma levels are
not obtained. Because metoclopramide stim-
ulates gastric emptying, it promotes absorp-
tion of ingested analgesic drugs and thus
facilitates pain relief.
If acetylsalicylic acid is administered i.v. as
the lysine salt, its bioavailability is complete.
Therefore, i.v. injection may be advisable in
acute attacks.
Should analgesics prove insuf ciently ef-
fective, sumatriptan (prototype of the trip-
tans) or ergotamine may help prevent an
imminent attack in many cases. Both sub-
stances are effective in migraine and cluster
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ache. The probable common mechanism of
action is a stimulation of serotonin receptors
of the 5-HT1D subtype. Moreover, ergot-
amine has af nity for dopamine receptors
(†nausea, emesis), as well as α-adrenocep-
tors and 5-HT2 receptors (⁄ vascular tone, ⁄
platelet aggregation). With frequent use, the
vascular side effects may give rise to severe
peripheral ischemia (ergotism). Paradoxi-
cally, overuse of ergotamine (> once per
week) may provoke “rebound” headaches,
thought to result from persistent vasodila-
tion. Though different in character (tension-
type headache), these prompt further con-
sumption of ergotamine. Thus, a vicious
circle develops with chronic abuse of ergot-
amine or other analgesics that may end with
irreversible disturbances of peripheral blood
flow and impairment of renal function.
Administered orally, ergotamine and su-
matriptan have only limited bioavailability.
Dihydroergotamine may be given by i.m. or
slow i.v. injection, sumatriptan subcutane-
ously, by nasal spray, or as a suppository.
When given orally, other triptans such as
zolmitriptan, naratriptan, and rizatriptan
have higher bioavailability than sumatrip-
tan.
Prophylaxis. Taken regularly over a longer
period, a heterogeneous group of drugs com-
prising propranolol, nadolol, atenolol, and
metoprolol (β-blockers), flunarizine (H1-his-
tamine, dopamine, and calcium antagonist),
pizotifen (pizotyline, 5-HT antagonist with
structural resemblance to tricyclic antide-
pressants), and methysergide (partial 5-HT
antagonist) may decrease the frequency, in-
tensity, and duration of migraine attacks.
The drug of first choice is one of the β-block-
ers mentioned.
 Migraine 335

A: Migraine and its treatment

Acetylsalicylic acid 1000 mg

or acetaminophen 1000 mg

When therapeutic effect inadequate

Sumatriptan or (Dihydro)-Ergotamine
and other triptans

6 mg 50–100 mg 1 mg 1–2 mg

Migraine Meto-
clopramide

Migraine attack:
Gastric emptying
Headache inhibited accelerated
Hypersensitivity of
olfaction, gustation,
audition, vision,
nausea, vomiting Drug
Neurogenic absorption
inflammation,
local edema, delayed improved
vasodilation

5-HT1B/1D Relief of migraine 5-HT1B/1D

5-HT1A Psychosis 5-HT1A

and other triptans

Ergotamine
Sumatriptan

D2 Nausea, D2
vomiting

5-HT2 Platelet aggregation 5-HT2

α1 + α 2 Vasoconstriction α1 + α 2

Luellmann, Color Atlas of Pharmacology © 2005 Thieme

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