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Molecular Targets For Drug Action (syllabus
-prof.Kršiak) FOUR MAJOR TARGETS FOR DRUGS 1.
RECEPTORS 2. ION CHANNELS 3. CARRIER MOLECULES 4.
ENZYMES
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Molecular Targets For Drug Action FOUR MAJOR
TARGETS FOR DRUGS 1. RECEPTORS 2. ION
CHANNELS 3. CARRIER MOLECULES 4. ENZYMES
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1. RECEPTORS
Channel-linked receptors
G-protein-coupled receptors
Cell Membrane
Kinase-linked receptors
RECEPTORS
Intracellular - Receptors linked to gene

transcription (nuclear receptors)
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CHANNEL-LINKED RECEPTORS (ionotropic receptors)
- about 90 of synapses in the CNS - for fast
synaptic transmission (msec) - examples NICOTINI
C, NMDA RECEPTOR Na flows into cells,
depolarization, excitation GABAA RECEPTOR Cl-
flows into cells, hyperpolarization, inhibition
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CHANNEL-LINKED RECEPTORS (ionotropic
receptors)
Nicotinic receptor
Katzung 2-12 ale radeji GABAA
Katzung BG, 2001
pentameric structure - five subunits form a
cluster surrounding a central transmembrane pore.
When acetylcholine binds, the channel pore opens.
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GABAA receptor
Benzodiazep. receptor
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G-PROTEIN-COUPLED RECEPTORS (metabotropic
receptors)

• - sites for action of about 45 of drugs
• - for slow synaptic transmission (seconds -
  minutes)
• examples beta-adrenergic receptors,
• muscarinic receptors
• - coupling

RECEPTOR - serpentine receptors a polypeptide
chain traverses the membrane seven times
G PROTEIN
EFFECTOR
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G-PROTEIN-COUPLED RECEPTORS(metabotropic
receptors)
Katzung Fig 2-14
Katzung BG, 2001
serpentine receptors a polypeptide chain
traverses the membrane seven times, the
extracellular terminal (NH2), the intracelullar
carboxyl terminal, sites for binding ligands,
G-protein
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G-PROTEIN-COUPLED RECEPTORS(metabotropic
receptors)
RECEPTOR
G PROTEIN - trimer, ?, ?, ? subunits ?
subunit GDP?GTP, GTPase aktivity stimulation
(GS) , inhibition (GI) of the effector
EFFECTOR
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G-PROTEIN-COUPLED RECEPTORS(metabotropic
receptors)

EFFECTOR
EFFECTOR
EFFECTOR
RECEPTOR
G-PROTEIN
beta
gama
Alfa GDP
Alfa GDP
Alfa GTP
Alfa GDP
Alfa GDP?GTP
eg. adenylyl cyclase Gs? beta-adrenergic
receptor Gi? mu opioid receptor
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G-PROTEIN-COUPLED RECEPTORS (metabotropic
receptors)
RECEPTOR
G-PROTEIN
2nd messengers
adenylyl cyklase ? cAMP
Proteinkinases
ENZYM
EFFECTOR
fosfolipase C ?IP3, DAG
ION CHANNEL
Ca release
Activation/inhibition of cellular functions eg.
contractile proteins, enzymes, transporters, ion
channels
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Molecular Targets For Drug Action) FOUR MAJOR
TARGETS FOR DRUGS 1. RECEPTORS 2. ION
CHANNELS 3. CARRIER MOLECULES 4. ENZYMES
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2. ION CHANNELS

• voltage-gated channels
• calcium channels - Ca flows into cells,
  calcium channel blockers
• sodium channels - Na flows into cells,
  blocked by local anaesthetics
• ligand-gated channels, G protein-gated, and
  other
• (directly or by intermediaries),

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Molecular Targets For Drug Action FOUR MAJOR
TARGETS FOR DRUGS 1. RECEPTORS 2. ION
CHANNELS 3. CARRIER MOLECULES 4. ENZYMES
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3. CARRIER MOLECULES

• pumps
• sodium pump - Na/K ATPase,
• pumps Na from the cell, inhibited by
  cardiac glycosides
• proton pump - H/K ATPase,
• pumps H from the cell , proton pump
  inhibitors
• transporters
• transporters for noradrenaline, serotonine
• inhibited by most antidepressants (RUI,
  TCA, SSRI etc)

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Molecular Targets For Drug Action FOUR MAJOR
TARGETS FOR DRUGS 1. RECEPTORS 2. ION
CHANNELS 3. CARRIER MOLECULES 4. ENZYMES
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4. ENZYMES sites of action of about 30 of drugs

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Molecular mechanisms of drug effects -
summary FOUR MAJOR TARGETS FOR DRUGS
Examples of drugs
perif. muscle relaxants
Channel-linked receptors
membr.
about 45 of drugs,e.g. beta-blockers
G-protein coupled receptors
1. RECEPTORS
Enzyme-linked rec.
intracelul.
Calcium ch. blockers
- Calcium chan.
Voltage gated
- Sodium chan.
lok. anaesthetetics
2. ION CHANNELS
Ligand-gated, G-prot.,
- sodium
cardiac glykosides
pumps
3. CARRIER MOLECULES
- proton
PP inhibitors
transporters
antidepressants
4. ENZYMES
ACE inhibitors, IMAO
ACE, MAO, COX, HMG-CoA reductase