Neuro Pharm II Flashcards
What should I know about serotonin production and structure?
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
What is the pathway for serotonin degradation and inactivation? Where is serotoninc produced in the CNS?
largely reuptake and degradation by MAO
Raphe nuclei
What should I know about serotonin receptors?
5HT1: inhibitory; decr. cAMP
5-HT2: G protein coupled; cause depol of cortical neurons
5HT3: ligand gated ion channel that causes depol
What are some functions of serotonin? What parts of the brain are involved (4)
sensory processing and regulation of sleep-wake (talamus and cortex
- homeostasis via autonomic centers
- pain sensation via spinal projections
- mediation of mood
What should I know about histamine (where produced, receptor type, main effects)?
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
What is the major excitatory transmitter in the brain?
glutamate- medaites all fast excitation in the CNS
What should I know about gluamate synthesis?
produced from alpha-ketoglutarate (part of Krebs cycle)
also can be synthesized from glutamine or aspartate
How is glutamate inactivated? What should I know about this process?
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
What are the 4 glutamate receptors? What are the receptor types?
NMDA, kainate, AMPA, metabotropic
NMDA, Kainate, AMPA are all ligand-gated ion channels. Metabotropic receptor is a G-protein coupled receptor.
What should I know about NMDA? (what ions, what are some features of channel)
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.
What should I know about the AMPA receptor? (what ions, what are some features of the channel)
permeable to Na and K.
depolarizes the membrane- may initiate an AP- opens voltage dependent Na and Ca channels
What should I know about kainate receptors? (what ions, what are some features of the channel)
permeable to Na and K. depol may cause an AP by opening voltage dependent Ca and Na channels
What should I know about the metabotropic receptor?
G-protein goupled to incr. IP3/DAG and PLC
increases intracellular Ca, like all glutamate receptors
What is the clinical relevance of glutamate?
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.
What are the inhibitory amino acids of the CNS?
principle inhibitory amino acid is GABA
glycine is neuroinhibitory and some brainstem and spinal cord pathways
What should I know about GABA production?
produced at the nerve terminal
enzyme is glutamic acid decraboxylase
converts glutamate to GABA via decarboxylation
Describe GABA inactivation.
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!
What is the precursor for glycine? How is it inactivated?
produced by serine breakdown
inactivated by Na-dependent reuptake
What are some major sites/cells of GABA in the CNS?
Very abundant. Esp in:
- inhibitory interneurons
- 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
What is the localization of neurons that use glycine?
Brain stem and spinal cord
What is an example of the use of glycine neurons?
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.
What are the two kinds of GABA receptors?
- 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.
What are important drugs that act on GABAa receptors? What do they do?
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.
What is strychnine?
rat poison that is a glycine receptor antagonist and causes severe tetanic convulsions of skeletal muscle.
What is picrotoxin?
GABA antagonist that leads to immediate seizures and death
