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Adenylate
cyclase type 2
GABAA receptor
Gamma-
aminobutyric
acid type B
receptor
N-type calcium
channel
G protein-
activated
inward
rectifier
potassium
channel 1
Substance-P
receptor
ATP-binding
cassette
sub-family C
member 3
Solute carrier
family 22
member 1
ATP-binding
cassette
sub-family C
member 3
Cytochrome P450
2D6
UDP-
glucuronosyltransferase
2B7
Mu-type opioid
receptor
Gβ
Gγ
γ-Aminobutyric acid
Substance P
Morphine
Codeine-6-glucuronide
cAMP
Ca
+
Ca
+
Na
+
Na
+
γ-Aminobutyric acid
Morphine
Morphine
Morphine
Codeine
Codeine
Codeine-6-glucuronide
Codeine-6-glucuronide
Codeine-6-glucuronide
ATP
PP
i
O
2
NADH
H
2
O
Formaldehyde
NAD
UDP-D-galacturonate
UDP
H
+
Heme
GTP
Pain
Guanine
nucleotide-
binding protein
G(i) subunit
alpha-1
Magnesium
Less GABA leads to
disinhibition of dopamine
cell firing in the spinal
chord pain transmission
neurons. This leads to
analgesia and less pain
signalling
Decreased calcium levels
lead to decreased
neurotransmitter release.
Less GABA is released for
synaptic vesicles.
Morphine and
codeine-6-glucouronide
activate presynaptic mu
opioid type receptors in the
dorsal root ganglion
The Gi subunit of the mu
opioid receptor activates
the inwardly rectifying
potassium channel increasing
K+ conductance. This causes
membrane hyperpolarization
decreasing the chances of
neuronal firing/action
potential.
Post-Synaptic Neuron
Pre-Synaptic Neuron
Synapse
Cytosol
Synaptic Vesicle
The mu opioid receptor
through the gamma subunit
inhibits voltage gated
N-type calcium channels
stopping the influx of
calcium into the neuron.
Morphine acts at A delta and
C pain fibres in the dorsal
horn of the spinal chord. By
decreasing neurotransmitter
action there is less pain
transmittance into the
spinal chord. This leads to
less pain perception.
C Pain Fibres
The inhibition of adenylate
cyclase prevents the
production of cAMP which
further prevents
depolarization and pain
signalling
Substance P is also not
released into the synapse
which prevents the
activation of pain
signalling.
Codeine is usually given
orally, but can also be
given subcutaneously or
through and intramuscular
shot.
Only 5% of codeine is
metabolized into morphine,
the majority is metabolized
into codeine-6-glucuronide
which is the main active
metabolite
Hepatocyte
Liver
Endoplasmic Reticulum
ADCY2
GABRG2
GABBR1
CACNA1B
KCNJ3
TACR1
ABCC3
SLC22A1
ABCC3
CYP2D6
UGT2B7
OPRM1
GNB1
GNG2
γ-Aminobutyric
acid
Substance P
Morphine
Codeine-6-
glucuronide
cAMP
Calcium
Calcium
Sodium
Sodium
γ-Aminobutyric
acid
Morphine
Morphine
Morphine
Codeine
Codeine
Codeine-6-
glucuronide
Codeine-6-
glucuronide
Codeine-6-
glucuronide
Adenosine
triphosphate
Pyrophosphate
Oxygen
NADH
Water
Formaldehyde
NAD