NSC 4363

where is histamine primarily produced?

tuberomammillary nuclei

another word for hypocretin

orexin

T/F

histamine receptors are auto receptors

T

histamine stimulation releases what?

orexin

T/F

histamine makes you sleep

F

histamine makes you awake

Narcolepsy is the loss of what production in the hypothalamus

orexin

antidepressants block the reuptake of ______ & reduce narcolepsy

NE

what reduces hypersomnolence by increases histamine

modafinil

receptor antagonist that treats insomnia

suvorexant

narcolepsy leads to ______ and ______

cataplexy

daytime sleepiness

histamine biosynthesis & degradation

histidine --→ histamine via HD

histamine --→ out of cell via vHAT

out of cell --→ tell-methylhistamine via (HAM-T)

blocks vHAT

tricyclics

HA can inhibit release of neurotransmitters post or pre?

pre

HA can affect arousal, memory, and learning post or pre

post

post via Gq

a) H1

b) H2

c) H3

d) H4

a

post via Gs

a) H1

b) H2

c) H3

d) H4

b

pre (as auto receptors) and post via Gi

a) H1

b) H2

c) H3

d) H4

c & d

all allergy medications use ____ receptors

H1 antagonist

Peripheral histamine that leads to inflammation

Peripheral histamine that leads to immune response

Peripheral histamine that releases gastric acid

H1R

H4R

H2R

allergy, anti-congestive, anti-inflammatory

a) peripheral H1 antagonist

b) peripheral H2 antagonist

c) CNS H1 antagonist

d) CNS H3 antagonist

a

antacids

a) peripheral H1 antagonist

b) peripheral H2 antagonist

c) CNS H1 antagonist

d) CNS H3 antagonist

b

anti-emetics, vertigo, sleep

a) peripheral H1 antagonist

b) peripheral H2 antagonist

c) CNS H1 antagonist

d) CNS H3 antagonist

c

alzeheimer therapy, nootropics, stimulants, ADD therapies, anti obesity

a) peripheral H1 antagonist

b) peripheral H2 antagonist

c) CNS H1 antagonist

d) CNS H3 antagonist

d

serotonin synthesis

L-tryptophan \---→ L-tryptamine via TrpH L-tryptamine \---→ serotonin via AAADC

serotonin degradation

5-HT \---→ 5-aldehyde via MOA-A 5-aldehyde --→ 5-HIAA via AD

rate limiting enzyme in serotonin biosynthesis

Trp H

T/F 5-HT receptors are pentameric, homo & hetero, and typically dimeric

T

which serotonin receptor(s) are ionotropic

5-HT3

which serotonin receptor(s) are metabotropic

5-HT 1,2,4-7

Auto receptor uses the alpha subunit Gi pathway a) 5-HT1 b) 5-HT2 c) 5-HT3

a

uses beta-gamma subunit VDCCs a) 5-HT1 b) 5-HT2 c) 5-HT3

a

uses apha subunit Gq pathway a) 5-HT1 b) 5-HT2 c) 5-HT3

B

Melatonin biosynthesis

serotonin --→ via 5-HT-N-acetylase N-acetylase-5-HT --→melatonin via 5-OH-indole-OMT

T/F serotonin blocks psychedelic effects and are also antischizophrenic

T

serotonin agonists used for migraine therapy

5-HT 1B&D ergotamine facial, cerebral, vasoconstrictors ends in triptan; sumatriptan

Indoiaminergic psychedelics

5-HT2 agonist LSD-25 psilocybin

hallucinogens and psychedelics bind to 4 things

D2 alpha 2 LSD serotonin receptors

SSRI agonists (antidepressants/anxiolytics/anti-OCD)

indatraline cocaine buspiron -5HT-1 agonist

SSRI antagonist (antidepressants/anxiolytics/anti-OCD) -increases catecholamine levels in the synapse by acting as an 5-HT reuptake inhibitor AND a noradrenergic reuptake inhibitor

venlafaxine duloxetine

antiemetics (prevent nausea) use what 2 things

5-HT3 antagonist ondansetron

Nootropics enhance \_____ and end in the suffix \_____ using this receptor

learning & memory setron 5-HT3

After you've had enough Serotonin for one day, it gets broken down in the pineal gland to form this molecule

melatonin

pathways

dorsal & medial raphe nuclei

where is NE produced?

locus coreulous

NE increases \______ \___and could lead to a heart attack

heart rate

“release blockers” block what ions making them lower blood pressure

hydrogen and magnesium ATPase protein pump

Name 3 classes of adrenoreceptors (NE & E)

Alpha: alpha 1: smooth muscle contraction- Gqalpha 2: smooth muscle dilation- Gi Beta B1,2,3: cardiac & smooth muscle contraction - Gs

MAO-inhibitors for DA and serotonin

befloxatone harmaline

MAO-inhibitors for DA and histamine

deprenyl

COMT-inhibitors for DA and histamine

tolcapone

MAO-inhibitors are often prescribed as

anti-depressants

Work as antidepressants, ADHD, and axiolytics

bupropion venlafaxine duloxetine intradaline

work as decongestants, eyedrops, and cause cotton mouth

alpha 1 adrenoreceptors agonists

treat high blood pressure & cross BBB

alpha 2 adrenoreceptors agonists

acts as bronchodilators name one short and long term one

beta adrenoreceptors agonists short- albuterol long- salmeterol

act as antihypertensive drugs

beta 1 adrenoreceptors antagonists

Catecholamine biosynthesis

Tyrosine \---→ L-Dopa using tyrosine hydroxylase L-Dopa --→ Dopamine using AADC

rate limiting step in the biosynthesis of catecholamines

tyrosine hydroxylase

medicine that blocks AADC in peripheral so it can reach the brain

carbidopa

T/F dopamine can cross the BBB

F

two central pathways for dopamine (DA) synthesis

substantia nigra ventral tegmental pathway

enzyme that turns dopamine to norepinephrine

DBH

enzyme that turns norepinephrine into epinephrine

DNMT

why are false transmitters useful?

act as a competitive buffer of dopamine so people who make too much dopamine can decrease its activity

key difference between transmitter and false transmitter

false transmitters begin with alpha-methyl

DA is degraded into \_______ via \_______

HVA MAO

exogenous vDAT inhibitor impairing DA to enter vesicles

reserpine

T/F Amphetamines are reuptake inhibitors

T

Name 2 ways amphetamines block reuptake

compete for DAT upregulate MAP-K, phosphorylate DAT, internalize DAT

dopamine receptors are all found \___synaptically while D2 are found in \___

POST both

D1&5 receptors use the what pathway to synthesize AC

Gs

D2-4 receptors use what pathway to synthesize PLC

Gi

T/F synaptic DAT is the main mechanism for DA synthesis

F synaptic DAT is the main mechanism for DA DEGRADATION

Name the dopamine neurotoxins

MPP+ 6-OH-DA

The dopamine neurotoxins do what?

kill DA neurons selectively and dose-dependently produce behavioral effects mimicking parkinson’s

DA (agonists/antagonists) for Parkinsons

apomorphine bromocriptine

DA (agonists/antagonists) for RLS

pramipexole ropinrole

DA antagonists are usually \_______ that affect what receptor.

neuroleptics D2

Neuroleptics that antagonize D2 receptors activate this pertussis toxin-sensitive G protein pathway

Gi

The two cholinergic receptor subtypes are

muscarinic and nicotinic

Functions in CNS & NMJ, ionotropic a) muscarinic b) nicotinic

b

Functions in CNS & peripheral Metabotropic a) muscarinic b) nicotinic

a

ACh biosynthesis and degradation steps

choline & acetyl coenzyme A \----→ ACh through ChAT ACh \----→ choline and acetate through AChE

what is the limiting reagent in ACh biosynthesis

choline

Name of drugs that inhibit activity of AChE causing an increase of acetylcholine

organophosphates or anticholinesterase

irreversible ligands that block ACh

DDT

long duration ligands that block ACh

diazinon malathion

nACHRs have at least 2 \_____ subunits

alpha

T/F nACHR have ACh gated Calcium channels

F nACHR have ACh gated sodium channels

nicotinic receptors have a common heteromeric structure comprising of what subunits

alpha 4 and beta 2

some nicotinic receptors are homomeric and are comprised of?

5 alpha 7 subunits changing the hill coefficient from 2 to 5

nACHR gating occurs via conformational change, explain the changes

closed state: hydrophobic side chains face sodium channel open state: 2 ACh binds and conformational change happen so hydrophilic side chains face sodium channels

nAChRs are postsynaptically found in the?

autonomic ganglia and NMJ

nAChRs are presynaptically found in the?

CNS

nicotine decreases \______ leading to \______ deprevation

glutamate glucose

first purified, sequenced, and cloned receptor

nAChR

When ACh receptor is activated repeatedly over time, they become \______ and \______ phosphorylation accelerates this

desensitized protein kinase

desensitization is (reversible/irreversible) using \______ which \______ the channel

reversible phosphate dephosphorylates

α7 nAChR antagonist often prescribed as an antidepressant and smoking cessation aid

bupropin

mAChRs 1,3,5 activate \___ which activates \___

Gq PLC