overview of neurotransmission and therpeutic target of CNS drugs

Neurone

• are a particular type of cell that carry information message or signals to and from the brain and the rest of the body

How do neurone work

• resting state

• Excited state

Resting state

• neurones stay at rest with their sodium ions on the outside of the cell body and potassium ion on the inside

Excited state

• neurons get excited with the sodium ions rush inside (from outside) and potassium ions rush out (from inside) the cell body

• This rushing in and out causes depolarisation and generates actions potential racing down the axon

How does sodium/ potassium move in/ out in the neurone

• active transport: sodium/ potassium ATPase pumps

• Ions channels

What is/ are the consequence of neurone firing

• once the electrical impulse reaches the terminal button (axon), it trigger the vesicles (containing neurotransmitter) to move towards the terminal end and release neurotransmitter into the synapse

• Neurotransmitters released from the pre-synaptic neurones bind to the receptor in the post synaptic neurone and activate downstream signalling

The released NT can do or more of the following

• AP generated opens the calcium channel int the pre synaptic neurone and regulates the trafficking, docking and fusion of neurotransmitters contains vesicles

• Bind to presynaptic receptor

• Bind to postsynaptic receptor

• Diffuse out of the synaptic cleft

• Metabolise/ degrade by enzyme

• Reuptake by the pre- synaptic transporter

Major CNS drugs target

• ion channels

• Metabotropic receptor

• NT reuptake transporter

• Enzyme

Ionotropic receptor

• ionotropic receptor are ligand gated ion channels that allow ion flow upon binding with specific neurotransmitters, enabling rapid synaptic tranasmission

Key features and properties of ion channel

• selective transmembrane pore

• Specific sensor for gating

• Regulatory mechanism

Advantages of allosteric drugs

• offers a novel pharmacological options of fine tuning receptor function

• Intensify a weakened hormone/ NT signal caused by localised deficit

• Clinically safer drugs with enhanced selectivity and reduced liability for receptor tolerance and/ or desensitation

Drugs altering neurotransmitter synthesis

• inhibits rate limiting enzyme

• Pro- drug substrate

• False substrate

Voltage gated ion channel- sodium channel

• the ion channel blockade is dependent on the rate of action potential discharge

• The following drug classes exhibit higher addinity for inactivated ion channel

Drugs altering NT metabolism

• neurotransmitters metabolism is mostly mediated via the enzymatic process