Drugs and Synaptic Transmission

synthetic drugs

scientists have created drugs artificially. These synthetic drugs are often more potent compared to their natural counterparts. Most drugs influence behaviour by influencing synaptic transmission (

Drugs that affect synaptic transmission are classified into two general categories:

1. Antagonists: A drug that opposes or inhibits the effects of a particular neurotransmitter on the postsynaptic cell (impedes between neuron communication)

1. Agonists: A drug that facilitates the effects of a particular neurotransmitter on the postsynaptic cell (facilitates between neuron communication)

 

Drugs Influence Synaptic Transmission 4 ways

Drugs can influence:

1. The way neurotransmitters are produced in the presynaptic neuron (synthesis)

2. How neurotransmitter molecules are stored in the presynaptic neuron

3. How neurotransmitter is released into the synapse

Drugs can influence neurotransmitter production

Neurotransmitters are produced in a neuron from precursor chemicals via the actions of enzymes (which control chemical reactions)

 

Precursor chemical = could be amino acids which are the building blocks for proteins

 

Enzymes = things that control chemical reactions

Some drugs act as precursor chemicals. They have an agonist effect because they facilitate neuronal communication

 

 

• Parkinson's Disease impacts some dopamine circuits in the brain.

• The drug levodopa (L-DOPA produced in a lab) can used to treat Parkinson's disease symptoms

• L-DOPA is precursor which can cross the blood brain barrier and be used by the brain to synthesise dopamine

 

 (L-DOPA

• Parkinson's Disease impacts some dopamine circuits in the brain.

• The drug levodopa (L-DOPA produced in a lab) can used to treat Parkinson's disease symptoms

• L-DOPA is precursor which can cross the blood brain barrier and be used by the brain to synthesise dopamine

 

Drugs can influence neurotransmitter production

• Other drugs can stop the synthesis of neurotransmitters from precursor chemicals.

• They have an antagonist effect because they impede neuronal communication

• These drugs stop the enzymes which help produce neurotransmitters from working as they normally would

 

 

 

 

The drug PCPA works by inhibiting the activity of an enzyme which the brain needs to produce the neurotransmitter serotonin

(PCPA is used in research to look at the effects of serotonin depletion on the nervous system)

PCPA

The drug PCPA works by inhibiting the activity of an enzyme which the brain needs to produce the neurotransmitter serotonin

(PCPA is used in research to look at the effects of serotonin depletion on the nervous system)

neurotransmitter are stored In

• Neurotransmitter molecules are stored in synaptic vesicles in the presynaptic neuron

• Following action potential, the vesicle fuses with the presynaptic membrane and releases neurotransmitter into the synapse

 

Drugs can influence how neurotransmitter are stored

Vesicle transporter proteins are located in the membrane of synaptic vesicles (just like the membrane of the terminal button) which transport neurotransmitter molecules

 

Some drugs can block the vesicle transporter proteins, such that neurotransmitter molecules cannot enter into the vesicle

 

• If there are no neurotransmitters in the vesicle at the time of an action potential, no neurotransmitter is released.

• This action inhibits neuronal communication, so these drugs have antagonist effects

Drugs can how neurotransmitters are released

• Some drugs can block the fusing of the synaptic vesicle with the presynaptic membrane.

 

• They deactivate proteins involved in fusing process and thus have an antagonist effect - they stop neurotransmitter being released into the synapse

 

 

• Other drugs encourage the fusing of the synaptic vesicle with the presynaptic membrane.

• They bind with proteins involved in this process and cause neurotransmitter release into the synapse.= encourage neuron communication

• These drugs therefore have an agonist effect

Postsynaptic Receptors

When neurotransmitter molecules attach to binding sites on receptor proteins (postsynaptic receptors), postsynaptic potentials are generated

Drugs and Postsynaptic Receptors 4 effecs

Drugs bind to binding sites on postsynaptic receptors and influence neuronal communication.

 

 Four different effects:

• Direct Agonist

• Direct Antagonist

• Indirect Agonist

• Indirect Antagonist

Direct Effects

Direct effects occur when drug molecules bind to a binding site on a receptor that neurotransmitter molecules normally bind with

 

Direct Agonists bind to receptor sites that neurotransmitters normally would bind to.

 

 Binding causes the opening of the ion channel which results in postsynaptic potentials.

 

 

Direct Antagonists (receptor blockers) bind to receptor sites that neurotransmitters would normally bind to.

Binding does NOT open the ion channel and blocks neurotransmitters from binding with the receptor site.

 

These actions stop the generation of postsynaptic potentials

Direct Agonists

bind to receptor sites that neurotransmitters normally would bind to.

 

 Binding causes the opening of the ion channel which results in postsynaptic potentials.

 

Direct Antagonists

Direct Antagonists (receptor blockers) bind to receptor sites that neurotransmitters would normally bind to.

Binding does NOT open the ion channel and blocks neurotransmitters from binding with the receptor site.

 

These actions stop the generation of postsynaptic potentials

Indirect Effects

Receptors can have more than one binding site.

 

 Indirect effects occur when drug molecules bind to one binding site on a receptor and neurotransmitter binds to another binding site on a receptor.

 

Indirect Agonist

• Indirect Agonists bind to one receptor site and work to facilitate the effect of the neurotransmitter attached to another receptor site to open an ion channel. When the ion channel is open, postsynaptic potentials occur.

Indirect Antagonists

bind to one receptor site and work to inhibit the effect of the neurotransmitter attached to another receptor site. The drug stops the neurotransmitter binding from opening an ion channel.
These actions stop the generation of postsynaptic potentials

Autoreceptors

• Autoreceptors are receptors on the presynaptic neuron

• Normally, neurotransmitter binding to autoreceptors causes less neurotransmitter to be released by the presynaptic neuron

 

 

Antagonist drugs bind to autoreceptors and decrease the production and release of neurotransmitters, which inhibits neuronal communication

 

Agonist drugs bind to autoreceptors and block them.

 As a result, this means that more neurotransmitter is produced and released, which enhances neuronal communication

 

Drug Effects on Neurotransmitter Reuptake and Deactivation (learning outcome 4)

• Reuptake occurs when a transporter protein located on the terminal button of the presynaptic neuron removes excess neurotransmitter from the synapse:

  

• Some agonist drugs can block the transporter protein and stop it from removing left over neurotransmitter in the synapse.

• If the neurotransmitter stays in the synapse for longer, neuronal communication is facilitated as it will continue to bind with postsynaptic receptors to cause postsynaptic potentials (changes in cellular charge).

 

• Enzymatic deactivation occurs when an enzyme deactivates neurotransmitter (breaks it down). Some agonist drugs can stop enzymes involved in the deactivation process from working.