Central Nervous System Neuropharmacology Flashcards Preview

Nervous System: Unit I > Central Nervous System Neuropharmacology > Flashcards

Flashcards in Central Nervous System Neuropharmacology Deck (21)
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1
Q

ACh: synthesis, storage, release, termination, receptors/trasduction mechanisms

A
  • synth: catalyzed by choline acetyl transferase
  • storage: in vesicles by vesicle-associated transporter (VAT
  • release: AP ==> Ca2+ release ==> fusion of vesicle
  • termination: degraded by AChE
  • receptors
    • muscarinic
      • M1 - M3 = Gq ==> stimulate PLC = excitatory
      • M2 - M4 = Gi/o ==> inhibits adenylyl cyclase = inhibitory
    • nicotinic: NN ==> ionotropic
2
Q

ACh: CNS location & function

A
  • location: produced @ cell bodies @ brain stem & basal forebrain
    • project into cebral cortex and hippocampus
  • fxn: coordinate movement and cognitive fxns
    • e.g. motivation, memory, learning
3
Q

ACh: pathophysiology

A
  • Alzheimer’s disease
  • Parkinson’s disease
  • Schizophrenia
4
Q

Monoamines: examples

A
  • Catecholamines
    • Dopamine
    • Norepinephrine
  • Indoleamines
    • Serotonin
5
Q

Catecholamine (DA & NE): synthesis, storage, release, termination,

A
  • synth: rate-limited tyrosine hydroxylase (TH)
  • storage: in vesicles by vesicle-monoamine transporter (VMAT) & protected from MOA (monoamine oxidase)
  • release: AP ==> Ca2+ release ==> fusion of vesicle
  • termination: reuptake by presynaptic transporters
    • DAT (Dopamine transporter)
    • NET (NE transporter)
  • receptors
    • NE
      • a1 = Gq ==> stimulate PLC = excitatory
      • a2 = Gi/o ==> inhibits adenylyl cyclase = inhibitory
      • b1 = Gs==> stimulate adenylyl cyclase
      • b2 = Gs ==> stimulate adenylyl cyclase
    • dopamine
      • D1 = Gs ==> stimulate adenylyl cyclase
      • D2 = Gi/o ==> inhibit adenylyl cyclase
6
Q

NE/DA: CNS location & function

A
  • location:
    • DA = substantia nigra => nestriatum pathway; ventral tegmental area => limbic cortex and frontel cortex; hypothalamus => pituitary
    • NE = cell bodies in pons/brainstem => all levels of brain
  • fxn:
    • DA = voluntary movement; reward-related behaviors; working memory & attention
    • NE = arousal, attention, vigilance, sleep-wake cycle; fear/anxiety; mood/emotion; modulate afferent pain
7
Q

NE: pathophysiology

A
  • Mania
  • Depression
  • Anxiety disorders
  • ADHD
8
Q

Indoleamine (5HT): synthesis, storage, release, termination, receptors/trasduction mechanisms

A
  • synth: rate-limited = tryptophan hydroxylase (TpH)
  • storage: in vesicles by vesicle-monoamine transporter (VMAT) & protected from MOA (monoamine oxidase)
  • release: AP ==> Ca2+ release ==> fusion of vesicle
  • termination: reuptake by presynaptic transporters
    • SERT (serotonin transporter)
  • receptors
    • 5HT4 = Gs ==> stimulate adenylyl cyclase
    • 5HT3 = ionotropic = excititatory
    • 5HT1A, 1B, 1D = Gi/o ==> inhibits adenylyl cyclase = inhibitory
    • 5HT2A, 2B, 2C = Gq ==> stimulate PLC = excitatory
9
Q

Indoleamine (5HT): CNS location & function

A
  • location: produced @ cell bodies @ raphe regions of pons/upper brain stem
    • project into all levels of brain
  • fxn:
    • sleep, arousal, attention
    • emotion/mood
    • pain pathways
    • eating/drinking behaviors
10
Q

Serotonin: pathophysiology

A
  • depression
  • anxiety disorders
  • schizophrenia
  • eating disorders
11
Q

NE/DA: CNS location & function

A
  • location:
    • DA = substantia nigra => nestriatum pathway; ventral tegmental area => limbic cortex and frontel cortex; hypothalamus => pituitary
    • NE = cell bodies in pons/brainstem => all levels of brain
  • fxn:
    • DA = voluntary movement; reward-related behaviors; working memory & attention
    • NE = arousal, attention, vigilance, sleep-wake cycle; fear/anxiety; mood/emotion; modulate afferent pain
12
Q

DA: receptors/trasduction mechanisms

A
  • dopamine
    • D1 = Gs ==> stimulate adenylyl cyclase
    • D2 = Gi/o ==> inhibit adenylyl cyclase
13
Q

NE: receptors/trasduction mechanisms

A
  • a1 = Gq ==> stimulate PLC = excitatory
  • b2 = Gs ==> stimulate adenylyl cyclase
  • b1 = Gs==> stimulate adenylyl cyclase
  • a2 = Gi/o ==> inhibits adenylyl cyclase = inhibitory
14
Q

DA: pathophysiology

A
  • schizophrenia
  • Parkinson’s disease
  • OCD
  • ADHD
  • drug abuse
15
Q

GABA: synthesis, termination, & receptors

A
  • synth: intertwined w/glutamate via GAD
  • termination: reuptake via GABA transporter
  • receptors:
    • GABAA: Opens ligand-gated Cl- channel (ionotropic) ==> IPSP
    • GABAB: Gi/o ==> inhibits adenylyl cyclase
16
Q

GABA: drug action targets

A
  • Benzodiazepines ==> bind GABAA receptors to facilitate GABA binding ==> increased inhibition @ postsynaptic cell
  • Tiagabine ==> inhibits reuptake of GABA
  • Vigabatrin ==> inhibits degradation by GABA-T
17
Q

GABA: CNS location & function

A
  • location: high concentration @ brain/spinal cord
  • fxn: major inhibitory transmitter in CNS
18
Q

GABA: Pathophysiology

A
  • generalized anxiety disorders
  • seizure disorders
  • sleep disorders
  • alcohol abuse & withdrawal
19
Q

Glutamate: synthesis & storage/release/termination

A
  • synthesis: glutamine ==> glutamate
  • termination:
    • reuptake by neuronal glutamate transporter
    • uptake by glial cell transporter ==> glutamate ==> glutamine by gultamine synthetase ==> neuron
20
Q

Glutamate: Receptors/transduction mechanisms

A
  • Ionotropic receptors
    • NMDA: Increase Ca++ influx
    • AMPA: Increase Na+ and Ca++ influx
    • Kainate: Increase Na+ influx
  • Metabotropic receptors:
    • R1-R5 (Group I): Gq ==> stimulation of PLC
    • R2-R3 (Group II): Gi/o ==> inhibition of adenylyl cyclase activity-inhibit VSCC-activate K+channels
    • R4-R6-R7-R8 (Group III): Gi/o  inhibition of adenylyl cyclase activity-inhibit VSCC
21
Q

Glutamate: Pathophysiology

A
  • epilepsy
  • ischemic brain damage
  • addiction
  • schizophrenia