Catecholamines

NSCI428 Exam 2

True or False: efficacy and potency are independent?

true

what is aripiprazole used to treat?

used to treat schizophrenia

does aripiprazole have high or low affinity?

high affinity, low efficacy

similarities between dopamine and norepinieprhine

chemical structures, agonists act as “stimulants”, some individual drugs act on both

How does aripiprazole compete with dompanie?

partial agonist for dopamine receptors

how dopamine is created?

tyrosine»tyrosine hydroxlyase»DOPA»aromatic amino acid decarboxylase(AADC)»Dopamine

where is dopamine synthesized?

at the axon terminals

4 different dopamine pathways

nigrostriatal, mesolimbic, mesocortical, and hypothalamic

Nigrostriatal dopamine pathway

substantia nigra»striatum

Dopamine release in the nigrostriatal pathway indicates what?

initiation of goal-directed movement

Mesolimbic dopamine pathway

VTA»nucleus accumbens

Dopamine release in the mesolimbic pathway indicates what?

pleasure and motivationn

Mesocortical dopamine pathway

VTA»frontal lobe

Dopamine release in the mesocortical pathways indicates what? 

cognitive, working memory

Hypothalamic dopamine pathway

hypothalamus»anterior pituitary gland

what does dopamine inhibit when it is acting as a hormone?

prolactin

how does dopamine get from the hypothalamus to the anterior pituitary?

travels a short difference through the bloodstream

how do antipsychotic drugs(raclopride) affect dopaminergic cells?

they inhibit the cells

how many subtypes of dopamine receptors are here

5

similarity of all dopamine receptors

all bind to dopamine

how do dopamine receptors vary?

location and other drugs they bind to

How are the dopamine receptors grouped?

2 subtypes

what are the two dopamine receptor groupings?

D1 like(D1 and D5) and D2 like (D2,D3,D4)

Are all the dopamine receptors metabotropic?

yes, they are all metabotropic

steps in neurotransmission

synthesis, transport, vesicle fusion, post-synaptic binding, degradation, reuptake

what breaks down dopamine?

catechol-O-methyltransferase (COMT) and/or monoamine oxidase (MAO)

how does phenelzine inhibit?

MAO

what is phenelzine?

Nardil, an antidepressant

What transports dopamine into vesicles?

VMAT2

What blocks VMAT2?

reserpine

How does reserpine affect dopamine pathways

blocks VMAT2 which depletes dopamine stores and causes sedation

how does MDMA affect serotonin?

prevents it from entering vesicles, sends it into synapse, leading to an increases of it in the synpase

what takes dopamine back to the presynaptic neuron?

dopamine active transporter (DAT)

what blocks DAT from moving dopamine into reuptake?

cocaine blocks the reuptake

how can amphetamine enter the cell?

by DAT or an NE transporter

how does amphetamine entering the cell affect dopamine?

causes dopamine to flow outward though it

Does amphetamine block DAT(or NE transporter)?

no it does not block it in the way cocaine does

what limits dopamine release?

autoreceptors limit its release

what kills dopaminergic neurons?

6-OHDA and MPTP

how does L-DOPA affect the dopaminergic system?

converted to dopamine in the brain

how does phenelzine affect the dopaminergic and noradrenaline system?

increases catecholamine levels by inhibiting MOA

how does AMPT affect the dopaminergic and noradrenaline system?

depletes catecholamines by inhibiting tyrosine hydroxylase

how does reserpine affect the dopaminergic and noradrenaline pathway?

depletes catecholamines by inhibiting vesicular uptake

how does 6-OHDA affect the dopaminergic pathway?

damages or destroys catecholaminergic neurons

how does amphetamines affect the dopaminergic and noradrenaline pathway?

releases catecholamines

how do cocaine and methylphenidate affect the dopaminergic and noradrenaline pathway?

inhibit catecholamine reuptake

how does apomorphine affect the dopaminergic pathway?

stimulates dopamine receptors (agonist)

how does SKF 38393 affect the dopaminergic pathway?

stimulates D1 receptors (agonist)

how does quinpirole affect the dopaminergic pathway?

stimulates D2 and D3 receptors (agonist)

how does SCH 23390 affect the dopaminergic pathway?

blocks D1 receptors (antagonist)

how does haloperidol affect the dopaminergic pathway?

blocks D2 receptors (antagonist)

what is synthesized from dopamine?

norepinephrine is synthesized

how norepinephrine is synthesized from dopamine?

dopamine»DBH»norepinephrine

peripheral nervous system

spinal nerves and cranial nerves

autonomic nervous sytem

includes the sympathetic and parasympathetic nervous systems

what does the locus coeruleus reach?

reaches every part of the brain (look at pic)

what are the main types of NE receptors?

alpha and beta

what does the alpha NE receptor affect?

contraction of blood vessels, uterine smooth muscles, bladder, spleen, and pupil

what does the beta NE receptor affect?

relaxation of heart, smooth muscle(bronchi and trachea), bladder,spleen, adipose tissue

what does NE’s role in arousal promote?

promotes wakefulness

PTSD

overconsolidation of bad memory

how can PSTD be treated?

treated with a Beta-blocker, propranolol

propranolol

antagonist for epinephrine and norepinephrine, can block reconsolidation

how does Nisoxetine affect noradrenaline system?

selectively inhibits NE reuptake

how does Phenylephrine affect the noradrenaline system?

stimulate alpha1-receptors (agonist)

how does clonidine affect the noradrenaline system?

stimulate alpha2-receptors (agonist)

how does albuterol affect the noradrenaline system?

stimulates beta receptors(partially selective for B2)

how does prazosin affect the noradrenaline system?

blocks alpha receptors (antagonist)

how does Yohimbine affect the noradrenaline system?

blocks alpha2 receptors (antagonist)

how does metoprolol affect the noradrenaline system?

blocks beta receptors (antagonist)