Mod 6- Introduction to the Pharmacology of CNS Drugs Flashcards
(55 cards)
First, it is clear that nearly all drugs with CNS effects act on
specific receptorsthatmodulate synaptic transmission.
A very few
agents such as _____________may have nonspecific
actions on membranes (although these exceptions are not
fully accepted), but even these non–receptor-mediated actions
result in demonstrable alterations in synaptic transmission.
general anesthetics and alcohol
The membranes of nerve cells contain two types of channels
defined on the basis of the mechanisms controlling their gating
(opening and closing): _______________
voltage-gated and ligand-gated channels
_____________ respond to changes in the membrane potential of the cell.
Voltage-gated channels
The_____________ described in Chapter 14 for the heart is an example of the first type of channel. In nerve cells, these channels are concentrated on the initial segment and the axon and are responsible for the fast action potential, which transmits the signal from cell body to nerve terminal.
voltage-gated sodium channel
There are many types of_______________ which act on a much slower time scale and modulate the rate at which the neuron discharges.
** voltage-sensitive calcium and potassium channels** on the cell body, dendrites, and initial segment,
Note : For example, some types of potassium channels opened by depolarization of the cell result in slowing of further depolarization and act as a brake to limit further action potential discharge.
Neurotransmitters exert their effects on neurons by binding to
two distinct classes of receptor.
- Ligand-gated channels or ionotropic receptors
- Metabotropic receptors
The first class is referred to as \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
The receptor
consists of subunits, and binding of ligand directly opens the
channel,which is anintegral parts of the receptor complex (see
Figure 22–6 ).
These channels are insensitive or only weakly sensitive
to membrane potential. Activation of these channels typically results in a brief (a few milliseconds to tens of milliseconds) opening
of the channel. Ligand-gated channels are responsible for fast
synaptic transmission typical of hierarchical pathways in the CNS
(see following text).
ligand-gated channels , or ionotropic receptors.
The second class of neurotransmitter receptor is referred to as \_\_\_\_\_\_\_\_\_\_\_\_\_.
These are seven-transmembrane G
protein-coupled receptors of the type described in Chapter 2 . The
binding of neurotransmitter to this type of receptor does not result
in the direct gating of a channel.
Rather, binding to the receptor
engages a G protein, which results in the production of second messengers
that modulate voltage-gated channels. These interactions
can occur entirely with the plane of the membrane and are referred
to as membrane-delimited pathways
metabotropic receptors
In this case,
the G protein (often the βγ subunit) interacts directly with the
voltage-gated ion channel.
In general, two types of voltage-gated ion
channels are the targets of this type of signaling: _______ and ___________
**calcium **channels
and potassium channels.
When G proteins interact with________________ they inhibit channel function. This mechanism accounts
for the presynaptic inhibition that occurs when presynaptic
metabotropic receptors are activated.
calcium
channels,
In contrast with G proteins when these receptors
are postsynaptic, they activate (cause the opening of )_________________, resulting in a slow postsynaptic inhibition.
potassium
channels
Metabotropic receptors can also **modulate voltage-gated channel**s less directly by the \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ ( Figure 21–2 D).
generation of diffusible second messengers
_______________ ( Figure 21–2 D).
A classic example Metabotropic
receptors can also modulate voltage-gated channels less directly is provided by the______________which generates cAMP via the activation of adenylyl cyclase (see
Chapter 2 ).
β adrenoceptor,
Whereas membrane-delimited actions occur within microdomains in the membrane, second messenger-mediated effects can occur over considerable distances.
Finally, an important consequence of the involvement of G proteins in receptor signaling is that, in contrast to the brief effect of ionotropic receptors, the effects of metabotropic receptor activation can last_____________
Metabotropic receptors predominate in the diffuse neuronal systems in the CNS (see below).
tens of seconds to minutes.
Mataba!
Mabagal kasi Mataba!!!
The events involved in synaptic
transmission can be summarized as follows.
An action potential in the presynaptic fiber propagates into the **synaptic terminalandactivates voltage-sensitive calciumchannels in themembrane of the terminal** (see Figure 6–3 ).
The calcium channels
- *responsible for the release of transmitter** are generally resistant **to the calcium channel-blocking agentsdiscussed in Chapter 12 (verapamil, etc) but aresensitive to blockade by certain marine toxins**
- *and metal ions** (see Tables 21–1 and 12–4 ).
Calcium flows into the terminal, and the increase in intraterminal calcium concentration promotes the fusion of synaptic vesicles with the presynaptic membrane.
The transmitter contained in the vesicles is released into the
synaptic cleft and diffuses to the receptors on the postsynaptic membrane.
** Binding of the transmitter to its receptorcauses abrief change **in membrane conductance (permeability to ions) of the postsynaptic cell. The time delay from the arrival of the presynaptic action potential to the onset of the postsynaptic response is approximately
This is the
resting membrane potential of the neuron.
–70 mV
Two types of pathways—
—impinge on the motor neuron.
excitatory and inhibitory
When an excitatory pathway is stimulated, a ___________________is recorded.
This potential is due to the excitatory transmitter acting on an
ionotropic receptor, causing anincrease in cation permeability.
Changing the stimulus intensity to the pathway, and therefore the number of presynaptic fibers activated, results in a graded change in the size of the depolarization. When a sufficient number of excitatory fibers are activated, the excitatory postsynaptic potential depolarizes the postsynaptic cell to threshold, and an all-or-none
action potential is generated.
small depolarizationor excitatory postsynaptic potential (EPSP)
When an inhibitory pathway is stimulated, the postsynaptic
membraneishyperpolarizedowing to theselective opening of
______________,producing aninhibitory postsynaptic potential
(IPSP) ( Figure 21–4 ).
However, because the equilibrium
potential for chloride is only slightly more negative than the resting potential (∼ –65 mV), the hyperpolarization is small and** contributes only modestly to the inhibitory action.**
chloride channels
A second type of inhibition is_____________
It was first described for sensory fibers entering the spinal
cord, where excitatory synaptic terminals receive synapses called
axoaxonic synapses (described later). When activated, axoaxonic synapses reduce the amount of transmitter released from the terminals
of sensory fibers.
presynaptic inhibition.
It is interesting that presynaptic inhibitory
receptors are **present on almost all presynaptic terminals in
the brain even though axoaxonic synapses appear to be restricted **to the _____________
In the brain, transmitter spills over to neighboring
synapses to activate the presynaptic receptors.
spinal cord.
Drugs acting on the synthesis, storage, metabolism, and
release of neurotransmitters fall into the________________.
presynaptic category
- *Synaptic transmission can be depressed by blockade of transmitter**
- *synthesis or storage.**
For example,____________depletes monoamine
synapses of transmitters by interfering with intracellular
storage. Blockade of transmitter catabolism inside the nerve terminal
can increase transmitter concentrations and has been
reported to increase the amount of transmitter released per
impulse.
reserpine
Drugs can also alter the release of transmitters. The
stimulant _____________induces the release of catecholamines
from adrenergic synapses
amphetamine
