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Ca
+
Tropomyosin
alpha-1 chain
Tropomyosin
beta chain
5-
hydroxytryptamine
receptor 2A
5-
hydroxytryptamine
receptor 2B
5-
hydroxytryptamine
receptor 1A
Voltage-
depenent L-type
calcium channel
Voltage-
depenent L-type
calcium channel
Voltage-
depenent L-type
calcium channel
Ryanodine
receptor 2
Sodium/calcium
exchanger 1
Voltage-gated
T-type calcium
channel (ICaT)
Voltage-gated
T-type calcium
channel (ICaT)
Voltage-
dependent
P/Q-type
calcium channel
subunit
alpha-1A
Voltage-
dependent
L-type calcium
channel subunit
beta-1
Voltage-
dependent
calcium channel
subunit
alpha-2/delta-2
Synaptic
vesicular amine
transporter
Sodium-
dependent
serotonin
transporter
Tryptophan
5-hydroxylase 1
Aromatic-L-
amino-acid
decarboxylase
Sarcoplasmic/endoplasmic
reticulum
calcium ATPase
2
cAMP-dependent
protein kinase
catalytic
subunit alpha
Ca
+
Serotonin
Serotonin
Methysergide
Methysergide
Methysergide
Ca
+
Ca
+
Ca
+
Na
+
Na
+
Ca
+
Ca
+
Ca
+
Ca
+
Serotonin
Methysergide
L-Tryptophan
Tetrahydrobiopterin
O
2
5-Hydroxy-L-tryptophan
4a-Hydroxytetrahydrobiopterin
CO
2
Na
+
Na
+
ATP
H
2
O
Ca
+
ADP
P
i
Ca
+
Fe2+
Pyridoxal
5'-phosphate
Ca
+
Troponin
Troponin
Muscle
Relaxation
GCPR signalling
pathway
GCPR signalling
pathway
Vascular endothelial cells
Sarcoplasmic Reticulum
Normally, calcium binding to
troponin displaces
tropomyosin from the myosin
binding sites on the actin
filaments. Low
concentrations of calcium
disallow this from
occurring.
Myosin and actin filaments
slide further away from each
other leading to muscle
relaxation.
Actin Filament
Myosin Filament
The 5-HT2 receptor is
coupled to Methysergide and
antagonizing this receptor
results in the G protein
signalling cascade not being
activated.
The G-protein signalling
cascade activates protein
kinase which activates
calcium channels on the
membrane, resulting in
calcium influx.
Low calcium cannot activate
the ryanodine receptor on
the sarcoplasmic reticulum.
Cytosol
Since calcium is linked to
activation of muscle
contraction. Reducing
cytosolic calcium levels
reduces muscle contraction
Methysergide acts by
narrowing blood vessels in
the brain and reduces blood
flow thereby alleviating
migraine symptoms
Synaptic Vesicle
Cytosol
Cytosol
Presynaptic Neuron
Postsynaptic Neuron
Synapse
↓ migraine and vascular
headaches
Serotonin is synthesized at
the raphei nuclei and stored
in synaptic vesicles at the
nerve terminal
Methysergide is an
antagonist on 5-HT2A, 5-HT2B
and 5-HT2C receptors and
exhibits vasoconstriction of
blood vessels and agonist at
5-HT1A receptors
Brain
Raphei nuclei producing
serotonergic neurons
Blood vessel - blood brain
barrier
passive diffusion
Methysergide is administered
orally