PHARMACOLOGY OF CNS DRUGS

Nearly all drugs with CNS effects act on specific receptors that modulates \________________.

transmission

True or False: CNS Drugs are among the most important tools for studying all aspects of CNS physiology.

True

True or False: Unraveling the actions of drugs with known clinical efficacy leads to the hypotheses regarding the mechanism of disease.

True

Neurons are supported by the \________________ through its foot processes.

astrocyte

\__________________ holds on to the blood vessels, prevents the excessive sodium, and will not allow drugs to readily affect the nervous cell.

Astrocytes

The axons of the neuron is protected by the myelin sheath formed by the \_______________ (in the CNS) or the \___________________ (in the PNS).

oligodendrocyte; schwann cells

True or False: The synapse physically comes in contact with one another.

False

The neural transmission will be transferred through several mechanisms. What are these mechanisms? (2)

Ion
Chemical

What act as receptors within the CNS? (2)

Ion Channels
Neurotransmitters

True or False: Most drugs that act on the CNS do so by changing ion flow through transmembrane channels of nerve cells.

True

What are the types of ion channels?

Voltage-gated
Ligand-gated

What are the three channels under Voltage-gated channel?

Potassium Channels
Sodium Channels
Calcium Channels

What are the four channels under Ligand-gated Channel?

- Nicotinic ACh receptor
- GABA(a) receptor
- Glycine receptor
- AMPA receptor

Tetrodotoxin and Batrachotoxin are under what voltage-gated channel?

Sodium Channels

Apamin and Charybdotoxin are under what voltage-gated channel?

Potassium Channels

Omega conotoxin (w-CTX-GVIA) and Agatoxin (w-AGAVIA) are under what voltage-gated channel?

Calcium Channels

This blocks channel from outside

Tetrodotoxin

This slows inactivation, shifts activation

Batrachotoxin (BTX)

Blocks "small Ca-activated" K-channels

Apamin

Blocks "big Ca-activated" K-channels

Charybdotoxin

Blocks N-type channel

Omega conotoxin (w-CTX-GVIA)

Blocks P-type channels

Agatoxin (w-AGAVIA)

What is the source of Tetrodotoxin?

Pufferfish

What is the source of Batrachotoxin (BTX)?

Colombian Frog

What is the source of Apamin?

Honeybee

What is the source of Charybdotoxin?

Scorpion

What is the source of Omega conotoxin (w-CTX-GVIA)?

Pacific cone snail

What is the source of Agatoxin (w-AGAVIA)?

Funnel web spider

α-Bungarotoxin acts on what receptor?

Nicotinic ACh receptor

Picrotoxin acts on what receptor?

GABAA receptor

Strychnine acts on what receptor?

Glycine receptor

Philanthotoxin acts on what receptor?

AMPA receptor

This substance is an irreversible antagonist.

α-Bungarotoxin

This substance blocks channel. (2)

Picrotoxin
Philanthotoxin

This substance is a competitive antagonist?

Strychnine

What is the source of α-Bungarotoxin?

Marine Shark

What is the source of Picrotoxin?

South Pacific plant

What is the source of Strychnine?

Indian Plant

What is the source of Philanthotoxin?

Wasp

The nerve cells contain two types of channels defined on the basis of the mechanism \___________________.

controlling their gating (opening & closing)

The type of channel that will close or open depending on the charge (inside and outside of the neurons).

Voltage-gated Channels

The type of channel that requires a chemical ligand that will bind to the binding site so that it would open or close the gates.

Ligand-gated Channels

Respond to changes in membrane potential

Voltage-gated Channels

The difference between the charge inside and outside the cell

Membrane Potential

The channels that are not directly affected by drugs.

Voltage-gated Channels

Voltage-gated ion channels are concentrated on what segment of the axons in the nerve cells?

Initial segment (axon hillock)

The channel responsible for fast action potentials?

Voltage-gated Ion Channels

The channels responsible for the action potential propagation.

Sodium Channels

Cell bodies and dendrites also have voltage-sensitive ion channels for \______________ and \________________.

Potassium; Calcium

What are the channels found in the axon?

Sodium Channels
Potassium Channels
Calcium Channels

Voltage-gated ion channels are affected by \______________, that is why it is not directly affected by drugs.

membrane potential

What are the two classes of neurotransmitter receptors?

Ligant-gated Channel
Metabotropic Receptor

These are the receptors that are affected by drugs.

Neurotransmitter Receptors

Drugs can mimic ligand to open and close the channel.

Ionotropic channel
Metabotropic receptors

This is a chemically-gated channel.

Ligand-gated Channels

This channel responds to chemical neurotransmitters (NTAs) that bind to receptor subunits of the channel.

Ligand-gated Channels

The ligand-gated ion channel responds to \___________________ that drugs mimic.

Endogenous neurotransmitters

The channels that are affected by drugs, exogenous and endogenous chemicals that mimic ligand to open and close channels.

Ligand-gated ion channel

Channels that are affected through extracellular binding sites (outside receptors).

Ligand-gated Ion Channels

Ligand-gated Ion Channels are also called...

Ionotropic Receptors

The receptor with the Seven transmembrane G protein coupled (Serpentine)

Metabotropic Receptors

Binding does not result in the direct gating of a channel; Binding engages the G-protein that results into production of second messengers that modulates the voltage gated channels intracellularly

Metabotropic Receptors

True or False: The metabotropic receptors indirectly affect the function of cells.

False

(Directly or indirectly)

Can either be:
○ Membrane-delimited regulation of ion channels
○ Diffusible second messenger-mediated regulation of ion channels

Metabotropic Receptors

Fill in the blanks:

metabotropic receptor → \_____________________ → \____________________________ → \______________________________

g protein; produce intracellular secondary messengers; affect intracellular ion channels through binding sites

What are the membrane delimited pathways?

Calcium Channels
Potassium Channels

Activation of the ligand-gated ion channel means that the gate is \___________.

Open

Inactivation of the ligand-gated ion channel means that the gate is \___________.

Closed

What are the three types of receptor channel coupling in ligand-gated ion channels?

1. A receptor that acts directly on the channel protein
2. A receptor that is coupled to the ion channel through a G protein
3. A receptor coupled to a G protein that modulates the formation of diffusible second messengers

What are the three second messengers that are modulated by a receptor coupled to a G protein?

a. cyclic adenosine monophosphate (cAMP)
b. inositol trisphosphate (IP3 )
c. diacylglycerol (DAG)

True or False: Influx of ions whether inside or outside the cell is an electrical mechanism to which synapse works.

True

Synapse is mostly for \_________________.

Communication

An ion current carried by the channel can either be... (2)

○ Excitatory Postsynaptic Potentials (EPSPs)
○ Inhibitory Postsynaptic Potentials (IPSPs)

This type of ion channel works by depolarizing potential change.

Excitatory Postsynaptic Potentials (EPSPs)

In a resting membrane, our membrane would be polarized by \_______________.

depolarizing

In depolarizing potential change, \______________ enters the cell.

positive

In Excitatory Postsynaptic Potentials (EPSPs), when your channels open, the tendency is the sodium channels \_________ and potassium channels subsequently \__________.

enter; react

Excitatory Postsynaptic Potentials (EPSPs) are generated by \________________ and \___________________.

Opening of sodium channels; closing of potassium channels

True or False: Originally, in the Excitatory Postsynaptic Potentials (EPSPs), the inside of the cell has a negative charge while the outside has a positive charge.

True

True or False: By opening channels, your positively charged sodium or calcium enters the cell and depolarizes it making it less negative.

True

True or False: Leaky potassium channels can be closed. This leads to potassium remaining inside the cell. Thereby increasing its positivity or lessening the negativity inside the cell until it may reach the threshold potential.

True

In the Excitatory Postsynaptic Potentials (EPSPs), there is an \_____________ in Na+, \_______________ in K+, and \_______________ in Ca+2.

increase; decrease; increase

The description below is observed in what role of the ion current (excitatory or inhibitory)?

Increase entry influx of sodium. As positive charge enters, it will become less negative (going higher in the graph). If you inhibit by closing potassium channels, it will accumulate the positive charge intracellularly thus causing excitatory potentials.

Excitatory Postsynaptic Potentials (EPSPs)

Depolarizing will make the charge more \____________.

positive

Hyperpolarizing will make the charge more \____________.

negative

Hyperpolarizing potential change to make our neuron more negative.

Inhibitory Postsynaptic Potentials (IPSPs)

This can be accomplished by opening a potassium or a chloride channel.

Inhibitory Postsynaptic Potentials (IPSPs)

In the Inhibitory Postsynaptic Potentials (IPSPs), there is an \_____________ in Cl- at the postsynaptic, \_______________ in K+ at the postsynaptic, and \_______________ in Ca+2 at the presynaptic.

increase; increase; decrease

Inhibitory potentials can also be generated in the presynaptic. It is done by \____________________.

decreasing the calcium influx or blocking calcium channels

It is through the entry of \_____________ where most neurotransmitters are secreted presynaptically.

calcium

True or False: al. However, if there is a summation, (several excitatory potentials coming from different communicating neurons) it may cause a higher depolarization thereby, allowing it to reach the threshold causing an action potential to be generated.

True

Several excitatory potentials coming from different communicating neurons

Summation

A type of summation that means "simultaneous" of different intensities.

Spatial

The type of summation that is subsequent, even before the full depolarization of the first excitatory potential, the second excitatory potential.

Temporal

What can reach the threshold potential, causing an action potential to be generated?

Higher baseline

Due to the lowering of the membrane potential, the usual excitatory potential that reaches the threshold will not be able to reach the threshold this time. This is observed in what type of potential?

Inhibitory postsynaptic potential

What is the mechanism of epileptic drugs? (Excitatory or Inhibitory)

Inhibitory postsynaptic potential

True or False: Some drugs exert their effect through direct interactions with molecular components of ion channels on axons.

True

What are some drugs that bind to the sites in the ion channels?

○ Carbamazepine
○ Phenytoin
○ Local anesthetics and some drugs used for general anesthesia

Most drugs exert their effect mainly our neural function at the \_____________.

Synapses