CNS Pharmacology

Neuron

electrically excitable cells that process and send information via electrochemical message

synapse

site of communication between a neuron and a target cell

other neuron componets

dendritesaxons

What are the 3 glial cells

astrocytes, oligodendrocytes, microglia

blood-brain barrier

protective functional barrier between the blood and the extracellular fluid of the CNS

what is the BBB made of?

tightly joined capillary endothelial cells and tightly joined surrounding layer of astrocyte feet

voltage gated channels respond to

changes in membrane potential

'voltage sensitive'

slower- some even slow an action potentialex. potassium and calcium channels

neurotransmitters can exert their effect on neurons through

binding to ionotropic receptors or metabotropic receptors

ligand-gated channels (ionotropic receptors)

-multiple subunits-neurotransmitter ligand directly opens the channel-activation results in brief opening of the channels

metabotropic receptors

-g-protein coupled receptors-ligand engages a G protein --> produces 2nd messengers --> cellular effect-often results on modulation of voltage gated channels

inhibitory pathway

post-synpatic is hyperpolarized due to incoming of chloride or exit of potassium due to opening of channels

neuronal systems two groups

hierarchical systems diffuse systems

hierchical systems

-pathways for sensory or motor-large myelinated fibers for fast conduction-projection & circuit neurons

projection neurons

-long axons that relay info over longer distances-usually activating -release glutamate-always excitatory

circuit neurons

-smaller neurons that remain in immediate vicinity-release GABA or glycine-always inhibitory

diffuse neuronal systems

-neuronal cell bodies in a limited number of places in the brain-branches from a single diffuse neuron may innervate different areas-fine and unmyelinated for slower conduction

neurotransmitters of the diffuse system

monoamines (such as norepinephrine) and acetylcholine

diffuse systems involved in

global functions (sleeping, waking, attention, emotional status)-longer lasting effects

Neurotranmitters

chemical substances that is released at the end of nerve fiber by the transmission of a nerve impulse and causes an effect

Glutamate: excitatory or inhibitory?

excitatory

ionotropic receptors

-AMPA-KA-NDMA

NDMA

-on almost all neurons in the CNS-highly permeable to K+, Na+, and Ca2+-more difficult to activate the nerve

inhibitory neurotransmitters

GABA and glycine

how do glycine and GABA receptors mediate effect

-hyperpolarize by influx of chloride ions-or block Na+/Ca2+ influx with K+ efflux

GABAa receptor

· Fast inhibitory response· Ionotropic receptors that open chloride channels

GABAb receptor

-slow and long-lasting inhibitory response-inhibits Ca2+ influx or opens K+ channels to allow efflux

M1 receptors facilitate

a slow excitatory response by decreasing permeability of K+ channels

M2 receptors facilitate

an inhibitory response by opening K+ channels

most CNS responses to acetylcholine are mediated by

muscarinic

dopamine receptors are

metabotropic

alpha 2 receptors

-In the locus coeruleus cause hyperpolarization in response to norepinephrine

alpha-1 and beta receptors

-in the brain facilitate and enhanced excitatory effect

norepinephrine is associated with

attention and arousal

all 5-HT3 subtypes are

metabotropic

5-HT3 receptors are

-ionotropic and have a rapid excitatory effect in limited areas in the brain

5-HT1A receptors are

often associated with strong inhibitory response by opening K+ channels for efflux

5-HT involved in

perception, mood, anxiety, pain, sleep, appetite, temperature, aggression and neuroendocrine control

histamine receptors are

metabotropic

histamine receptors modulate

arousal, attention and memory

Substance P excitatory or inhibitory?

excitatory

substance P associated with

pain and nausea

orexin

-excitatory effect-associated with wakefulness

endocannabinoids can travel

backward in the synaptic cleft and results of inhibition of neurotransmitter release

CB1

-high levels in brain-may produce short or long lasting inhibition-activated by THC

pre-synaptic effects

o Drugs that affect synthesis, storage, metabolism, and release of neurotransmitters

post synaptic effects

o Drugs that affect post-synaptic receptors as agonists or antagonists to augment neurotransmitter responses