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60 Cards in this Set

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How do most CNS drugs act?
alter synaptic transmission
AND
modulate effects of neurotransmitters
How do a few CNS drugs act?
voltage-gated ion channels
Dale's hypothesis?
Is it true?
Neurons use only one transmitter.

True for classical transmitters only.
Neuropeptides are co-transmitters in many cells.
3 criteria for "transmitter"
1. Presence- in presynaptic nerve terminals with its substrate and synthesizing enzyme
2. Release- release in response to depolarizing stimuli is CALCIUM dependent
3. Pharmacologic identity- effects of transmitter when applied experimentally must = effects of stimulating presynaptic pathway
Give 3 examples of small transmitters
ACh
Amines- DA, NE, Epi, Serotonin
Amino acids- glutamate, GABA, Glycine
Give 2 examples of peptide transmitters
opiods
NPY
Give 2 examples of transmitter gases
N2O
CO
How does an ionotropic receptor work
transmitter binds multimeric ligand-gated ion channel -->
increased permeability to one or more ions -->
either EPSP or IPSP
AMPA glutamate receptor
excitatory inotropic
kainate glutamate receptor
excitatory ionotropic
NMDA glutamate receptor
excitatory ionotropic
GABA receptor
inhibitory ionotropic
How do metabotropic receptors work
transmitter binds receptor bound to G-proteins -->
activates second messengers (IP3, DAG)
-->
modulate cellular physiology
Metabotropic glutamate receptor
metabotropic receptor
(if it were only that easy)
GABA-beta receptor
metabotropic receptor
alpha and beta adrenergic receptors
metabotropic receptors
Most excitatory synapses use...
glutamate
Glutamate transporters that take up glutamate are dependent on which ion?
Na
Where is glutamine made?
Nerve terminal mitochondria
Name three ligand gated ion channels/ionotropic receptors.
AMPA
kainate
NMDA
Other names for metabotropic glutamate receptors?
mGluR1-8 receptors
Which mGluR type(s) couples with G proteins and activates the IP3 system via PLC?
Type I
Which mGluR type(s) inhibit AMP synthesis by adenylyl cyclase?
Types II and III
Other than ligand binding, what else does the NMDA receptor need?
membrane depolarization
How does the NMDA receptor work?
increases intracellular Ca --> act as second messenger
Name five correlations to the NMDA receptor
1. learning and memory
2. ischemic neuronal damage
3. epileptic seizures
4. PCP psychosis
5. ketamine anesthesia
What is the major inhibitory neurotransmitter in the CNS?
GABA
How is GABA made?
From glutamate using GAD (glutamic acid decarboxylase) (w/ PP(vit B6))
What is GABA release dependent on?
Ca
Where does GABA work?
presynaptic autoreceptors and postsynaptic receptors
Which GABA receptor(s) are ionotropic, increase chloride ion conductance?
GABA-A and GABA-C
Which GABA receptor(s) are metabotropic?
GABA-B
Active GABA uptake into presynaptic endings and glia is dependent on which ion?
Na
What does GABA-T do?
Turns GABA into glutamine in mitochondria
Which GABA receptor is both presynaptic and postsynaptic?
GABA-B
Which GABA receptor has multiple binding sites for neuroactive drugs?
GABA-A
Name 3 agonists for GABA-A receptors?
1. Benzodiazepines- allosterically enhance GABA binding
2. Ethanol- enhances Cl channel opening
3. General anesthetics- bind hydrophobic site
Name 4 GABA-A antagonists; what can they cause?
1. bicuculline
2. picrotoxin
3. pentylenetetrazol
4. penicillin

seizures
Describe how GABA-B presynaptic receptors work
G/Go --> block Ca channel --> dec presynaptic Ca --> inhibit transmitter release
Nama a GABA-B presynaptic receptor agonist
Baclofen- centrally acting muscle relaxant (spasmolytic)
Describe how GABA-B postsynaptic receptors work
G/Go --> open K channel --> hyperpolarizes neuron --> inhibits depolarization
What is 5-hydroxytryptamine, 5HT
Serotonin
How is serotonin made?
tryptophan --> 5-hydroxytryptophan --> 5-hydroxytraptamine
Which areas of the CNS are involved with serotonin?
Raphe nuclei send serotonergic projections to --> cerebral cortex, limbic system, and diencephalon
What is serotonin release dependent on?
What increases the release?
Ca

fenfluramine
What types are most of the 15 different serotonin receptors?
pre and postsynaptic metabotropic (GPCRs)
What terminates action of serotonin? What can stop that?
active re-uptake into presynaptic terminals

SSRIs- fluoxetine, etc
What enzymatically degrades serotonin
MAO
How does LSD work?
inhibits firing of serotonin neurons --> reduces release of 5HT --> acts at presynaptic autoreceptors and modulates serotonin release
What is the excitatory neurotransmitter in the spinal cord?
ACh
Name two nicotinic receptor (ionotropic) agonists
ACh
nicotine
Name one nicotinic receptor (ionotropic) antagonist
curare
Name 2 muscarinic receptor (metabotropic) agonists
ACh
muscarine
Name 2 muscarinic receptor (metabotropic) antagonists
Atropine
Scopolamine
What may serve as a retrograde transmitter from postsynaptic to presynaptic cell?
NO
How is NO made?
Arginine --> NO + citrulline
via NO synthase
What activates NO synthase?
calcium-calmodulin
How can NO enhance transmitter release?
activates heme-containing gyanylyl cyclase
Where in the CNS is NO involved?
cerebellum
Name two correlations to CNS NO?
1. learning and memory
2. ischemic neuronal damage