10-15 NeuroPHARM: Transmitters and Receptors Flashcards
NMDA receptors:
MOA?
Modulators?
NDMA receptor MOA:
Modulators: glutamate
Match the following items:
- -excitation
- -inhibition
- -inward Ca2+
- -inward Cl-
- -inward Na+
- -depolarization
- -hyperpolarization
DEPOLARization ——> EXCITation w/ inward Na+ and Ca2+ flow
HYPERpolarization ——>INHIBition w/ inward Cl- flow
What’s the AP threshold? RMP?
AP thresh = -40mV
RMP = ~ -70mV
What do neurotransmitters modulate?
the AP threshold
EPSP and IPSP
excitatory post-synaptic potential and inhib…
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
2 G-protein coupled receptors are ONLY metabotropic
Name the different classes of neurotransmitter
Amino acids (e.g. GABA, glutamate)
ACh
Monoamines (Dopa, NE, serotonin)
Others (e.g. histamine, cannabinoids, adenosine, opioids, endorphins…)
Which Amino Acid neurotransmitters are inhibitory? Excitatory?
Inhib are NEUTRAL amino acids: GABA, glycine
Excit are ACIDIC amino acids: glutamate, aspartate
What is the major excitatory NT in CNS?
glutamate
Glutamate: effect? where made? binds what receptors? excess? deficiency?
—EXCITATORY —secreted by pyramidal cells —binds both ionotropic (main=AMPA also NMDA, Kainate) and metabo receptors —excess = excitotoxicity —deficiency may lead to schizophrenia
Tell me about the ionotropic glutamate receptors
-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
metab glutamate receptors?
signal via GPCR —> ∆s intracellular Ca2+ or adenyl cyclase —> cAMP
- also memory
- Agonists of Group II ? tx anx & schizo
GABA (gamma-aminobutyric acid):
- inhib or excitatory?
- where made?
- binds what receptors?
- role?
- drugs affecting?
- clinical action?
- 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
GABA(A)
- type?
- subunits?
- drugs?
—ionotropic (ligand gated ion channel)
—GABA—>α-subunit—>Cl- influx—>hyperpol—> inhib
—barbiturates bind β-sub
—benzos bind between α-γ
GABA(B)
- type?
- drugs?
—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
GABA(C)
- type?
- drugs?
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
Acetylcholine is: ...mainly excit or inhib? ...neurotransmitter for? ...bound by what receptors? ...enzymes involved include?
—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
nicotinic receptors
—Ionotropic Opens Na+ —> depolarization (EPSP)
—CNS and periphery in mammals
o Agonists: nicotine (addictive, anxiolytic, analgesic, increases alertness); epibatidine*, & choline
*analgesic frog poison
Muscarinic Receptors
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)
Name some AChE inhibitors
for dementia/AD: donepezil (Aricept), tacrine, galantamine, rivastigmine
**pesticides, nerve gases
What are the subclasses of monoamines?
catecholamines: dopamine, NE, epi
tryptamines: 5-HT, melatonin
histamine
Dopamine: —inhib or excite? —made from/in? —activates which/what receptors? —involved in? —degraded by?
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
Dopamine receptor families w/ mech?
—D1 Family (D1, D5) increases adenylyl cyclase —> excitat.
—D2 Family (D2, D3, D4) increases PDE and —> inhibit.
Dopamine receptor pathways?
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
Dopaminergic drugs for Parkinson’s?
L-Dopa
COMT inhibs
DOPA decarboxylase inhibs
DA agonists
Methylphenidate MOA?
dopamine reuptake inhibitor
Amphetamines
Induces DA release
Cocaine
prevent DA reuptake
Antipsychotics (e.g. clozaril)
D2 Receptor Antagonists
Norepi —made from/in? —activates what receptors? —involved in? —degraded by? —reuptake by?
—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)
clonidine: MOA, type and indications
—α2 agonist
—works both pre-and post-synaptically
—Neuropathic pain, opioid detoxification, ADHD, Tourette’s
5-HT (Serotonin) —made from/in? —activates what receptors? —metab or iono? —involved in? —degraded by? —reuptake by?
—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
TCA MOA?
tricyclics block serotonin transporter (SERT)
sumatriptan MOA
5-HT(1B)
ondansetron MOA
5-HT(3)
psychedilc MOA (LSD, ecstacy, peyote)
5-HT(2A)
Histamine
—receptors
—neuro effects?
H1-4
H1 —> imp for arousal (?JXC: drowsiness with anti-histamines)
Purinergic receptors:
- -types?
- -subunits?
- -drugs?
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)
Cannabinoids
—receptors
—neuro effects?
—agonists?
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
Opiods —receptors —neuro effects? —Drugs? —endogenous agoninsts?
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)
