Pharmacology-CNS Neurotransmitters Flashcards
Most CNS drugs target different steps in the nerve terminal or at the synaptic cleft. What are the specific targets of drugs designed for the CNS step?
1) Ion channels 2) Synthesis 3) Storage 4) Metabolism 5) Release 6) Reuptake 7) Degradation 8) Post-synaptic receptors 9) Downstream effectors.
What types of CNS drugs are especially fast acting?
Drugs that target VG ion channels and ligand-gated ion channels
What ion channel drugs can last from hours to days in the CNS?
Drugs that target the G-proteint coupled receptor. These drugs act slower because there are intermediates that need to form in order to open ion channels. Additionally, effects can be prolonged if the secondary messengers turn on transcription factors.
What are the 3 types of amplification?
Signal amplification (signal produces many diffusible messengers), space amplification (signal is not only limited to receptor site like GPCRs) and time amplification (longer lasting signal like TF that get turned on)
What is the most prevalent excitatory neurotransmitter in the CNS?
Glutamate
How is glutamate cleared from the nerve terminal after release?
Either the presynaptic nerve terminal takes it up via the glutamate transporter or glial cells take it up, turn it into glutamine and send it back to the neuron as glutamine where it will then be turned back to glutamate by glutaminase in the mitochondria.
What are the four types of glutamate receptors?
Matabotropic (presynaptic AND postsynaptic GPCR), KAR & AMPAR (Na+ flows in and K+ flows out depolarizing the cell and EPSP) and NMDAR (Ca2+ & Na+ in and K+ out)
What is required to activate the NMDA receptor?
Binding of glutamate AND glycine or serine. Also, the cell must depolarize to get ride of Mg2+ blocking the channel.
What are most inhibitory neurotransmitters in the CNS?
GABA
How is GABA synthesized and deactivated?
GABA is made from glutamate by glutamic acid decarboxylase (GAD). It is then packaged and secreted from the nerve terminal. GABA transporters take GABA back up either into the nerve terminal or into a glial cell. In the nerve terminal it can be repackaged or deactivated by GABA-transaminase in the mitochondria. In the glial cell it is deactivated by GABA-transaminase.
What are the two main types of GABA receptors?
GABA-A receptors (ionotropic receptor that allows Cl- entry into the cell, hyper polarizing the cell). GABA-B receptors (Presynaptic GPCR: inhibits adenylyl cyclase, increases K+ efflux from cell and decreases Ca2+, hyperpolarizing the cell and decreasing neurotransmitter release. Postsynaptic GPCRs: inhibit adenylyl cyclase and allow K+ to leave the cell, hyperpolarizing it)
How are dopamine, NE and EPI created from tyrosine?
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Where are the main dopaminergic systems in the brain? What type of receptors are these?
Substantia nigra and ventral tegmentum. All dopamine receptors are GPCR (metabotropic)
How is dopamine packaged, taken up and degraded at the nerve terminal?
Synthesized from Tyr. Loaded into vesicles by monoamine transporters (VMAT). Taken up by DAT and catabolized by MAO and COMT
How is serotonin (5HT) synthesized from tryptophan?
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What anatomic regions of the brain are most affected by serotonin?
Cerebral cortex, limbic system and diencephalon
Where to most serotonergic pathways originate in the brain?
Raphe nuclei, pons and upper brainstem
How is serotonin (5HT) released, taken up and deactivated at the nerve terminal?
Synthesized from tryptophan. Packed into vesicles by VMAT. Taken up by 5HT transporters (SERT). Catabolized by MAO.
What type of receptors are the majority of the serotonin (5HT) receptors?
14 are metabotropic (GPCRs) and some are excitatory, some inhibitory. 1 is the 5HT3 ionotropic receptor that allows Na+ and K+ flow, mediating EPSPs.
What are the opioid peptides?
Enkephalin, endorphin and dynorphin
What peptide mediates pain signaling?
Substance P
What type of stimulus do you need in a neuron that releases neuropeptides?
Strong. The release sites are often far away from the calcium-rich synaptic cleft.
What type of neurons are neuropeptides often secreted from?
GABA secreting neurons
How do storage, action, release site and receptors differ between classical neurotransmitters and neuropeptides?
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How do endocannabinoids differ from the other neurotransmitters?
They are not stored in vesicles. They come from lipid precursors that form the endocannabinoids when Ca2+ comes into the postsynaptic neuron. They are then released and act on GPCRs CB1 and CB2 which inhibits neurotransmitter release from the presynaptic neuron.
