Different Drug Effects on Synaptic Transmission

Agonist

Facilitates neuronic communication

Indirect Agonist / Antagonist

Does not work directly on the receptor

1 - Precursor (Indirect Agonist)

Drugs can serve as precursors, enhancing dopamine communication

• L-DOPA is a precursor for Dopamine, if you get enough of it, transforms into Dopamine

• Used for Parkinson’s (don’t have enough L-DOPA, or Dopamine)

4 - Drug Stimulates the Release of Neurotransmitters (Indirect Agonist)

Ex: Black widow spider venom released ACh into the synaptic cleft

• It opens calcium channels to release acetylcholine

6 - Drug Stimulates Postsynaptic Receptors (Direct Agonist)

Nicotine attaches directly to the nicotinic receptor

• Inotropic channel; receptor is involved in voluntary movement of muscles

Muscarine attaches directly to muscarinic receptor

• It can enhance movement directly

Direct Agonist / Antagonist

Does work directly on the receptor

9 - Drug Blocks Auto-Receptors from doing their job (indirect agonist)

Increases the release of neurotransmitter (the neuron won’t stop releasing it)

Ex: Idazoxan

• Blocks the auto-receptor of norepinephrine, so it continues to be released into the synaptic cleft

  • Extreme alertness, jitteriness, severe anxiety, etc

10 - Drug Blocks Re-uptake (indirect Agonist)

Ex: Cocaine blocks the re-uptake of dopamine

• Dopamine stays in the synaptic cleft and continually binds to the postsynaptic neuron (overstimulating the cell)

11 - Drug inactivates Acetylcholinesterase (Indirect Agonist)

Turns off enzymatic deactivation; stops acetylcholine from being broken down

• Ex: Physostigmine blocks acetylcholine from being broken down

Antagonist

Impedes or prevents neural communication

2 - Drug Inactivates Synthetic Enzymes (Indirect Antagonist)

Inhibits the synthesis of neurotransmitters

• Ex: PCPA decreases the concentration of serotonin (decreases enzymatic tranfer)

3 - Drug Prevents Storage of Neurotransmitters in the Synaptic vesicles (Indirect Antagonist)

Ex: Reserpine impedes the storage of monoamines (they cant be packaged)

• Dopamine, serotonin, norepinephrine, and epinephrine wont be released into the synaptic cleft

Channels in the synaptic vesicles get blocked (so transporters can package or release neurotransmitters into the synaptic cleft)

Drug inhibits the release of neurotransmitters (indirect Antagonist)

Ex: Botulinum Toxin

• A very potent bacterial toxin; a teaspoon could paralyze five boroughs

• Blocks acetylcholine from releasing (no moving, no moving, no heart muscle movement, which is death)

• Does not allow calcium channels to open

• Toxins can be severely diluted to become Botox (to stop face muscles from moving)

7 - Drug Blocks Postsynaptic Receptor (Direct Antagonist)

Ex: Curare

• If hit with an arrow dipped in this, become paralyzed

• Blocks the nicotinic receptor site (no acetylcholine reaches the postsynaptic neuron)

Ex: Atropine

• Vasodilator

• Dilated pupils sends unconscious signals to someone that you’re attracted to them

8 - Drug stimulates Auto-receptors; Inhibits neurotransmitter release (Indirect Antagonist)

Ex: Apomorphine

• Binds to the dopamine auto-receptor (stimulates it) and shits off the release of dopamine

Noncompetitive Binding

1. The neurotransmitter binds at one site; other drugs bind at a different site

2. Indirect agonists and antagonists act on an alternative binding site and modify the effects of the neurotransmitter on opening of the ion channel

Noncompetitive Agonist (PAM)

Result is increased neurotransmitter effect

• Ex: Xanax binds at one site while GABA binds to its receptor site

• Result is synergy: Both together keep the ion channel open longer, leading to longer effects

Noncompetitive Antagonist (NAM)

Result is reduced neurotransmitter effect

• Ex: Ketamine, glutamate is bound to its receptor and ketamine is bound at its own site which impedes the release of glutamate

• Without glutamate you dissociate or lose consciousness