CNS I: Introduction to CNS pharmacology Flashcards
What is beneficial about pharmaceutically targeting enzymes (over receptors)?
Don’t have to worry about densitization and can block synthesis or degradation.
What are the six neuronal systems in the CNS?
- Cognitive processing
- Memory
- Emotional processing
- Sensory processing
- Motor processing
- Autonomic processing
What are the three main differences between the CNS and ANS?
- Circuitry of CNS is more complex
- More synapses in CNS
- CNS uses more than 50 different NT
Describe the blood brain barrier and the types of drugs that can cross it
- Tight junctions between modified endothelial cells
- Astroglial processes and pericytes (pericytes and smooth muscle do the same thing)
Very lipophilic or small (eg. lithium) drugs can get through the BBB
When GABA receptors are activated, what is the ion flow across the membrane?
- Chlorine ion in
- Potassium out
Describe the functions of the following cellular organizations in the CNS:
- Long tracts
- Local circuits
- Divergent
Long tracts (relay/projection neurons)
- Messages over long distances
- Motor control
- Usually excitatory (glutamate)
Local circuits (interneurons)
- Short, modulating
- Eg. shape recognition in optic tract or horizontal cells in retina
- Usually inhibitory (GABA)
Divergent
- Widely projecting neurons
- Global functioning
- Sleep wake cycles
Give the four criteria to be a neurotransmitter
- Present at high concentration at synapse (localized)
- Released by chemical or electrical stimulation by a Ca dependent mechanism
- Produce postsynaptic response similar to nerve stimulation (synaptic mimicry)
- Mechanism of termination of transmitter action present
Give the 5 types of neurotransmitters in the CNS
Amino acids
- GABA/glycine/glutamate
Acetylcholine
Monoamines
Peptides
Endocannabinoids
List the glutamate receptors and the method for glutamate termination. (5)
- NMDA
- AMPA
- Kainate
- mGluR1 (postsynaptic, Gq)
- mGluR2,3 (presynaptic, Gi)
Termination is via glia uptake
List the GABA receptors (2). Which one can be presynaptic?
GABAa (ionotropic, pentameric channel)
GABAb (metabotropic, Gq with phospholipase C or adenyl cyclase). Closes Ca channels and opens potassium channels to reduce NT release presynaptically.
GABAb can be presynaptic
What type of receptor does glycine have? Where is glycine most expressed in the CNS?
Ionotropic chloride channel
Limited expression in interneurons and brainstem
Where does GABA bind on GABAa? Where do barbiturates and benzodiazepines bind?
GABA: Orthosterically, between α and β subunits of the 4 transmembrane units (2 alpha and 2 beta)
Exogenous ligands bind allosterically (not on active site)
Describe the actions of M1 and M2 muscarinic receptors
M1: Postsynaptic excitation
M2: Presynaptic inhibition with potassium channels
List the monoamines and where their final synthetic step occurs.
- Dopamine
- NE
- 5-HT
Synthesized in small amounts in the presynaptic terminal.
Describe dopamine receptors
5 known receptors, either D1 like or D2 like. Almost all metabotropic and generally inhibitory. Generally diffuse.
D1 like: More cAMP = IP3, DAG and calcium influx
D2 like: Less cAMP, less potassium influx
