Neuro Pharm II

Question 1

What should I know about serotonin production and structure?

Answer 1

indole amine
made from tryptophan by a process similar to synthesis of catecholamines (starts with tryptophan hydroxylase)
serotonin production increases with increased conc. of tryptophan

Question 2

What is the pathway for serotonin degradation and inactivation? Where is serotoninc produced in the CNS?

Answer 2

largely reuptake and degradation by MAO

Raphe nuclei

Question 3

What should I know about serotonin receptors?

Answer 3

5HT1: inhibitory; decr. cAMP
5-HT2: G protein coupled; cause depol of cortical neurons
5HT3: ligand gated ion channel that causes depol

Question 4

What are some functions of serotonin? What parts of the brain are involved (4)

Answer 4

sensory processing and regulation of sleep-wake (talamus and cortex

2. homeostasis via autonomic centers
3. pain sensation via spinal projections
4. mediation of mood

Question 5

What should I know about histamine (where produced, receptor type, main effects)?

Answer 5

produced in the lateral tuberomammillary nucleus of the hypothalamus (not bolded)
H1 receptors are G-protein coupled and activate PLC to incr. Ca and PKC.
anti=histamines may blockade these receptors and cause sedation, so histamine may be involved in arousal

Question 6

What is the major excitatory transmitter in the brain?

Answer 6

glutamate- medaites all fast excitation in the CNS

Question 7

What should I know about gluamate synthesis?

Answer 7

produced from alpha-ketoglutarate (part of Krebs cycle)

also can be synthesized from glutamine or aspartate

Question 8

How is glutamate inactivated? What should I know about this process?

Answer 8

gluamate is inactivated by reuptake by neurons and by astrocytes. In astrocytes, glutamate is converted to glutamine. glutamine can be taken up by neurons and converted back to glutamate. this inactivation process is very important, because high or persistant levels of glutamate are neurotoxic- excitotoxicity

Question 9

What are the 4 glutamate receptors? What are the receptor types?

Answer 9

NMDA, kainate, AMPA, metabotropic

NMDA, Kainate, AMPA are all ligand-gated ion channels. Metabotropic receptor is a G-protein coupled receptor.

Question 10

What should I know about NMDA? (what ions, what are some features of channel)

Answer 10

ligand gated Na, K, Ca channel.
slow to open and close
also requires activation by glycine
voltage-sensitive: Mg2+ blocks the channel pore at resting membrane potentials. When cell is depolarized, the MG block is relieved.

Question 11

What should I know about the AMPA receptor? (what ions, what are some features of the channel)

Answer 11

permeable to Na and K.

depolarizes the membrane- may initiate an AP- opens voltage dependent Na and Ca channels

Question 12

What should I know about kainate receptors? (what ions, what are some features of the channel)

Answer 12

permeable to Na and K. depol may cause an AP by opening voltage dependent Ca and Na channels

Question 13

What should I know about the metabotropic receptor?

Answer 13

G-protein goupled to incr. IP3/DAG and PLC

increases intracellular Ca, like all glutamate receptors

Question 14

What is the clinical relevance of glutamate?

Answer 14

may be involved in learning and memory
but, high levels lead to calcium dependent neuronal death (excitotoxicity). May mediate injury with stroke, and may play a role in neurodegenerative diseases like Huntington’s.

Question 15

What are the inhibitory amino acids of the CNS?

Answer 15

principle inhibitory amino acid is GABA

glycine is neuroinhibitory and some brainstem and spinal cord pathways

Question 16

What should I know about GABA production?

Answer 16

produced at the nerve terminal
enzyme is glutamic acid decraboxylase
converts glutamate to GABA via decarboxylation

Question 17

Describe GABA inactivation.

Answer 17

rapid reuptake by neurons and astrocytes
In astrocytes can go through GABA shunt: GABA endters Krebs cycle, leaves as alpha-ketogluterate, is converted to glutamate. Glutamate converted to glutamine, which is transferred to presynaptic neuron and converted back to glutamate. Glutamate is a precursor for GABA!

Question 18

What is the precursor for glycine? How is it inactivated?

Answer 18

produced by serine breakdown

inactivated by Na-dependent reuptake

Question 19

What are some major sites/cells of GABA in the CNS?

Answer 19

Very abundant. Esp in:

1. inhibitory interneurons
2. Major inhibitory pathways, like the cerebellar Purkinje projections to deep cerebellar nuclei and GABA-ergic projections from the striatum to the globus pallidus and the substantia nigra

Question 20

What is the localization of neurons that use glycine?

Answer 20

Brain stem and spinal cord

Question 21

What is an example of the use of glycine neurons?

Answer 21

Renshaw cells: feedback loop. Renshaw cells inhibit alpha motor neurons that are also receiving excitatory input from glutamenergic neurons. this rapid on/off is important for sensory discrimination and fine motor control.

Question 22

What are the two kinds of GABA receptors?

Answer 22

• Ligand-gated chlorine channels (GABAa and GABAc). GABAc is found in the retina only. Cause rapid hyperpolarization.
• GABAb: G protein coupled receptor that inhibts cAMP ofration or activates voltage dependent K channels. Cause slow synaptic inhibition.

Question 23

What are important drugs that act on GABAa receptors? What do they do?

Answer 23

Benzodiazepines (diazepam): increase chlorine conductance through the channel by increasing the probablility of channel opening after GABA binding.
used to treat anxiety and as sedatives and anti-seizure meds
Barbituates (phenobarbitol) and alcohol keep the channel open for longer.

Question 24

What is strychnine?

Answer 24

rat poison that is a glycine receptor antagonist and causes severe tetanic convulsions of skeletal muscle.

Question 25

What is picrotoxin?

Answer 25

GABA antagonist that leads to immediate seizures and death