Basic Principles of Neurobiology and Neuropharmacology Flashcards
___ ____ contains storage vesicle which contain NTs which are released into the synapse.
terminal branches
Communication within a neuron is ___. Between neurons is ____
Communication within a neuron is ELECTRICAL . Between neurons is CHEMICAL.
synthesis (production of NTs) requires ___ and ___
requires substrates and enzymes.
turnover
overall rate at which the whole NT store within a given neuron is replaced
activity label
directly related to the amount of binding to receptor sites.
receptors on a post syn neuron have a ___ and ___ fit
lock and key fit: highly specific to particular chemical configurations of a specific neurotransmitter that is release by the presyn neuron.
NTs only bind if they match the chemical configuration of the receptor.
2 basic presynaptic receptors
1) autoreceptors: involved in feedback. moedulates activity of the NT being released.
2) heteroreceptors: activated by other neurons.
majority of post synaptic receptors are ___ ____ receptors.
SERPENTINE PROTEIN RECEPTORS: they exhibit a transmembrane protein structure: spans the cell membrane back and forth 7 times.
receptors a susceptivle to ligand-induced sensitization/desensitization. What does this meaN?
receptors can become unresponsive or sensitive as a result of repeated and prolonged NT binding.
receptor sites are normally occupied by a ____ NT, but drugs can initiate a cellular response similar to or identical to that exerted by the NT.
endogenous NT
agonistic action
when something is introduced to produce an increase in activity level, or that mimics the response to the endogenous NT.
Ex/ emphetamine is an NE agonist, it increases the activity level of a neuron through increased adrenergic receptor activity.
antagonist
binding to a receptor site normally occupied by an NT, but not initiating a transmitter-like action, blocks access of the NT to its binding site. Ie/ antagonist is an inhibitor. interferes/depresses activity level.
general rule of psychopharmacology
drugs do not create any unique effects, they merely modulate normal neuronal function ing (agonizing or antagonizing actions of NT)
3 major processes of how a neuron controls activity –> “system modulation”
1) reuptake: NTs released are sponged up by the presynaptic neuron and restored in storage vesicles. Allows for recycling of NTs.
- ACTIVE PROCESS continually occurring.
- DECREASES activity level by REDUCING [NT]
- occurs AFTER the NT has excited or inhibited the receiving cell and detaches from the receptor site. then the NT gets taken back up.
2) presynaptic feedback
- utilizes AUTORECEPTORS on the presyn membrane
- released NT binds to presyn receptor sites. neuron responds by increasing or decreasing further release of the same NT into synaptic gap.
3) enzymatic inactivation (Catabolism)
- enzymes breakdown the NT in the synaptic cleft so it cannot exert effects at receptors.
- decreases activity by breaking down NT
- MAO found in synaptic cleft AND presyn membrane. COMT methyltransferase is also an enzyme that deactivates NT.
- level of metabolites is an indicator of NT activity.
- metabolites can be found in CSF, blood, urine.
Reuptake accomplishes 2 things:
1) decreased [NT] in synaptic membrane to decrease activity
2) recycles/reuses NT
metabolite of NE
MHPG
metabolite of DA
HVA
metabolite of 5HT
5-HIAA
chatecholamine, indolamine andAA NTs
CA: DA + NE
IA: 5HT
AA: glut, GABA.
Draw out the metabolic pathway for catecholamines including the metabolites
see notes. Hard to type out
Draw out the metabolic pathway for 5HT including its metabolite after breakdown
see notes.
AMPT is a _____ ____ inhibitor. What does this implicate AMPT in
its a TYROSINE HYDROXYLASE inhibitor. Therefore, it is a DOPA SYNTHESIS INHIBITOR. Net effect of AMPT is that it prevents the production of DA and NE, thus lowers activity of the DA and NE systems by preventing the rate limiting step of catecholamine metabolism
rate limiting step in catecholamine metabolism/breakdown
Tyr –> DOPA via tyr hydroxylase
DBH inhibitors
inhibits dopa beta hydroxylase, preventing DA metabolism into NE.
Less activity – storage vesicles are not releasing as much NE (they are not as full because NE is not being produced), and thus there are less NE in the synapse to bind all the receptors/exerting less effect.
reserpine
blocks the storage of catecholamines. Less catecholamine activity by depleting the availability by reduing NT in storage vesicles.
cocaine
blocks reuptake of Da/NE. More Da is available in synaptic gap. More DA lingering in GAP = more binding = more activity.
-cocaine is an agonist, a stimulant.
amphetamine:
1) increases release of DA/NE
2) some direct stimulation of post syn. receptors.
both result in more DA/NE in gap, therefore more activity.
Methamphetamine.
best fit on receptors. more potent than amphetamine. Neurotoxicity is a major issue.
1) increases release of DA/NE
2) some direct stimulation of post syn. receptors.
more activity, even more release of DA/NE
LSD
Catecholamine post syn receptor AGONIST: LSD binds to the catecholamine receptor: chemically mimics catecholamine.
- increased binding on post syn receptor site, resulting in MORE ACTIVITY
Buproprion
DA/NE uptake inhibitor, leaving more CA in the gap because they cannot be taken out of the synaptic cleft. MORE ACTIVITY. Da/Ne agonist.
two trade names of buproprion
1) welbutrin (antidepressant)
2) zyban (smoking cessation)
MAOIS:
inhibits the activity of MAO. Prevents the breakdown of catecholamines. DA/NE agonist. Net effect of MAOI is an increase in activity because an increase of availability of NT in the gap.
- used as an antidepressant: Nardil, Phenelzine.
LDOPA
enantiomer/isomer of DOPA. Can still act as DOPA in catecholamine metabolism pathway. Dopa decarboxylase can still act on LDOPA to crease DA.
therefore, LDOPA is an agonist to the Da/NE pathway. Increased Da/NE in synaptic cleft because more is being made. Therefore morea ctivity.
DA Post synaptic receptor blockers
Competitive reversible blockers.
- DA antagonist. blocks DA receptor.
therefore, reduces activity.
-competes for post syn receptor sites with DA in gap
-less binding of DA to post syn repeptors= antagonist = less activity.
uses of a DA post synaptic receptor blocker
Schizophrenia
Chlorporomazine, Haloperidol are examples of DA post syn receptor blockers
Parachlorophenylalanine
5HT synthesis inhibitor by blocking tryptophan hydroxylase. Results in less 5HT being made, stored, and thrown out into the gap to bind to 5HTR.
SSRIs
5HT uptake inhibitors. An Agonist, Increased activity by increased 5HT in gap. Increases availability of 5Ht in the gap, results in more activity. Used as antidepressAnt (fluoxetine). Paxil also a common SSRI.
Fenfluramine
increases releases of 5HT. Therefore it is an agonist that increases activity of a 5Ht system because there is increased 5Ht in the synaptic cleft.
- used in appetite supression. But it has significant side effects.
LSD (indolamine effects)
5HT post syn receptor agonist. Binds to post syn receptor and stimulates it in the way 5Ht does. Results in more activity of serotonergic pathways.
When does reuptake occur
occurs AFTER the NT has excited or inhibited the receiving cell and detaches from the receptor site. then the NT gets taken back up.
