10-15 NeuroPHARM: Transmitters and Receptors

Question 1

NMDA receptors:
MOA?
Modulators?

Answer 1

NDMA receptor MOA:

Modulators: glutamate

Question 2

Match the following items:

• -excitation
• -inhibition
• -inward Ca2+
• -inward Cl-
• -inward Na+
• -depolarization
• -hyperpolarization

Answer 2

DEPOLARization ——> EXCITation w/ inward Na+ and Ca2+ flow

HYPERpolarization ——>INHIBition w/ inward Cl- flow

Question 3

What’s the AP threshold? RMP?

Answer 3

AP thresh = -40mV

RMP = ~ -70mV

Question 4

What do neurotransmitters modulate?

Answer 4

the AP threshold

Question 5

EPSP and IPSP

Answer 5

excitatory post-synaptic potential and inhib…

Question 6

Which of these statements is false?

1) Ionotropic receptors involve direct opening of ion channels
2) G-protein coupled receptors can be both ionotropic and metabotropic
3) Secondary messengers are required for signaling through metabotropic receptors
4) Na+ and K+ commonly pass through ion channel receptors to alter membrane potential

Answer 6

2 G-protein coupled receptors are ONLY metabotropic

Question 7

Name the different classes of neurotransmitter

Answer 7

Amino acids (e.g. GABA, glutamate)
ACh
Monoamines (Dopa, NE, serotonin)
Others (e.g. histamine, cannabinoids, adenosine, opioids, endorphins…)

Question 8

Which Amino Acid neurotransmitters are inhibitory? Excitatory?

Answer 8

Inhib are NEUTRAL amino acids: GABA, glycine

Excit are ACIDIC amino acids: glutamate, aspartate

Question 9

What is the major excitatory NT in CNS?

Answer 9

glutamate

Question 10

Glutamate:
effect?
where made?
binds what receptors?
excess?
deficiency?

Answer 10

—EXCITATORY
—secreted by pyramidal cells
—binds both ionotropic (main=AMPA also NMDA, Kainate) and metabo receptors
—excess = excitotoxicity
—deficiency may lead to schizophrenia

Question 11

Tell me about the ionotropic glutamate receptors

Answer 11

-Na+ selective channel
——NMDA, main one, allows in Ca2+, too
-needs glycine as co-agonist
-must be depolarized to work (blocked by Mg2+ @ RMP)
-antagonists: PCP, ketamine
-crit for synaptic plasticity, network assoc., memory

Question 12

metab glutamate receptors?

Answer 12

signal via GPCR —> ∆s intracellular Ca2+ or adenyl cyclase —> cAMP

• also memory
• Agonists of Group II ? tx anx & schizo

Question 13

GABA (gamma-aminobutyric acid):

• inhib or excitatory?
• where made?
• binds what receptors?
• role?
• drugs affecting?
• clinical action?

Answer 13

• INHIBITORY
• made by interneurons from glutamate via glutamic acid decarboxylase (GAD)
• GABA(A), GABA(B) and GABA(C)
• benzos, barbiturates, EtOH, general anesthetics
• anxiolytic, musc relax, anesthesia, anti-sz, sedation
• *may be excitatory in utero/in neonates

Question 14

GABA(A)

• type?
• subunits?
• drugs?

Answer 14

—ionotropic (ligand gated ion channel)
—GABA—>α-subunit—>Cl- influx—>hyperpol—> inhib
—barbiturates bind β-sub
—benzos bind between α-γ

Question 15

GABA(B)

• type?
• drugs?

Answer 15

—metabotrop —> causes nearby Ca2+ channel closure and K+ opening (K+ efflux)—>hyperpol—> inhib
—baclofen is selective GABA(B) agonist; antiplasticity tx in ALS and MS

Question 16

GABA(C)

• type?
• drugs?

Answer 16

AKA GABA(A-ρ_ receptor (only have one subunit-ρ)
—Ionotropic —> Opens Cl- Channels (inhib)
—High expression in retina, spinal cord and pituitary
—**Not modulated by benzos, barbiturates, or baclofen

Question 17

Acetylcholine is:
...mainly excit or inhib?
...neurotransmitter for?
...bound by what receptors?
...enzymes involved include?

Answer 17

—mainly EXCITatory
—neurotrans for NMJ, parasmyp, CNS
—bound by Nicotinic (ionotrop w/ Na+) and muscarinic M1-M5 receptors (GPCR, metab)
—made by ChAT (decr in AD); degraded by AChE

Question 18

nicotinic receptors

Answer 18

—Ionotropic Opens Na+ —> depolarization (EPSP)
—CNS and periphery in mammals
o Agonists: nicotine (addictive, anxiolytic, analgesic, increases alertness); epibatidine*, & choline

*analgesic frog poison

Question 19

Muscarinic Receptors

Answer 19

M1, M3, M4, M5: CNS
M2: Heart
M3: smooth muscle
Antagonists: Atropine (M1-5; mydriatic; ACLS); Scopolamine (M1; motion sickness, salivation)
Agonists: Muscarine (M1-M2), carbachol
(M1-5), Pilocarpine (M3; glaucoma)

Question 20

Name some AChE inhibitors

Answer 20

for dementia/AD: donepezil (Aricept), tacrine, galantamine, rivastigmine
**pesticides, nerve gases

Question 21

What are the subclasses of monoamines?

Answer 21

catecholamines: dopamine, NE, epi
tryptamines: 5-HT, melatonin
histamine

Question 22

Dopamine:
—inhib or excite?
—made from/in?
—activates which/what receptors?
—involved in?
—degraded by?

Answer 22

Dopamine:
—D1&5: EXCITE; D2,3,4: INHIB
—made from/by/in L-tyrosine in VTA and sub nigra
—activates D1-D5 metabo. GPCRs
—involved in behavior, cognition, motor activity, motivation, reward, addiction
—degraded by COMT and MAO

Question 23

Dopamine receptor families w/ mech?

Answer 23

—D1 Family (D1, D5) increases adenylyl cyclase —> excitat.

—D2 Family (D2, D3, D4) increases PDE and —> inhibit.

Question 24

Dopamine receptor pathways?

Answer 24

1) Nigrostriatal (Subs. Nigra—>striatum)—>Parkinson’s
2) Mesolimbic (VTA—>N.accumbens, amygdala)—> Schizophrenia, Addiction
3) Mesocortical (VTA—>[?PF]Cortex)—>Schizophrenia
4) Tuberoinfundibular (Hypothalamus—>pituitary) = steroid effects

Question 25

Dopaminergic drugs for Parkinson's?

Answer 25

L-Dopa COMT inhibs DOPA decarboxylase inhibs DA agonists

Question 26

Methylphenidate MOA?

Answer 26

dopamine reuptake inhibitor

Question 27

Amphetamines

Answer 27

Induces DA release

Question 28

Cocaine

Answer 28

prevent DA reuptake

Question 29

Antipsychotics (e.g. clozaril)

Answer 29

D2 Receptor Antagonists

Question 30

``` Norepi —made from/in? —activates what receptors? —involved in? —degraded by? —reuptake by? ```

Answer 30

—Made from L-Tyrosine via Dopamine in Locus Coeruleus,Caudal Raphe Nucleus —Activates Metabotropic (α/β adrenergic receptors) —> ∆s intracellular cAMP —Involved in arousal, attention, focus. **Disorders:depression,ADHD,phobias,pain **Main NT in symp sys —Degraded by MAO and COMT —Reuptake by NET (NE Transporter)

Question 31

clonidine: MOA, type and indications

Answer 31

—α2 agonist —works both pre-and post-synaptically —Neuropathic pain, opioid detoxification, ADHD, Tourette’s

Question 32

``` 5-HT (Serotonin) —made from/in? —activates what receptors? —metab or iono? —involved in? —degraded by? —reuptake by? ```

Answer 32

``` —made from L-tyrptophan —activates 5-HT(1-7) receptors —5-HT1&2: metab; 5-HT3 iono, excitatory —involved in anger, aggression, mood, sleep, sexuality, appetite, pain —degraded by MAO —reuptake by SERT ```

Question 33

TCA MOA?

Answer 33

tricyclics block serotonin transporter (SERT)

Question 34

sumatriptan MOA

Answer 34

5-HT(1B)

Question 35

ondansetron MOA

Answer 35

5-HT(3)

Question 36

psychedilc MOA (LSD, ecstacy, peyote)

Answer 36

5-HT(2A)

Question 37

Histamine —receptors —neuro effects?

Answer 37

H1-4 | H1 —> imp for arousal (?JXC: drowsiness with anti-histamines)

Question 38

Purinergic receptors: - -types? - -subunits? - -drugs?

Answer 38

types = P1 & P2 P1 - Adenosine receptor, modulate cAMP, blocked by caffeine —A1: decr HR —*A2A*: conorary vasodilation, **decr DA** —A2B: bronchoconstriction —A3: smm constric; card musc relax P2 = ADP, ATP receptors, IONOtropic —P2x: mod synap transmiss (nociception/pain) ——effect on muscle contract (heart SMM of vas def) —P2y: metabo (GCPR)

Question 39

Cannabinoids —receptors —neuro effects? —agonists?

Answer 39

metabotropic GCPR —CB1: inhib GABA (inhibiting the inhibition of DA) ——anandamine: endogenous CB1 agonist that attenuates pain, present in chocolate ——∆9-tetrahydrocannabinal; cannabidiol (anti-psychotic) —CB2: immune system

Question 40

``` Opiods —receptors —neuro effects? —Drugs? —endogenous agoninsts? ```

Answer 40

Opioid receptors are metabotropic —Mu, Delta, Kappa, nociceptin —Effect depends on receptor and opioid —Endogen.: endorphins, enkephalins, dynorphins (may be inv w/ drug abuse, antidepressant activity and chronic pain)