5 - Transporters and targets of drug action Flashcards
What is a primary active transporter
Na/K ATPase
What is a secondary active transporter
Plasma membrane glutamate transporter (all NT transporters)
Where are neurotransmitter transporters found
Post- and pre-synaptic neurones and glial cells
What are the two main neurotransmitter families
Glutamate and Neurotransmitter sodium symporter (NSS)
What do the NSS family transport (5)
GABA Glycine Dopamine Noradrenaline Serotonin
How many subtypes of EAATs are there
5
Where is EAAT4 mainly expressed
Cerebellum
Where is EAAT5 mainly expressed
Retina
Which EAAT transports L-Cysteine as well
EAAT3
In the transporter homologue (EAAT) from Pyrococcus horikoshii, how many subunits were there
3
What is GLTph
A Na+ dependent aspartate transporter
What are all human NSS coupled to
Na and Cl
How do GlyT1 inhibitors work to treat schizophrenia
In schizophrenia there is reduced NMDAR activity
Inhibition of GlyT1 will elevate excitatory synapses and stimulate NMDAR
What are GlyT2 inhibitors used to treat
Reduce transmission of pain signals from spinal cord up to the brain
What shape are dDat transporters
Shot glass shape
What does dDAT rely on the co-transport of
2 Na and 1 Cl ion
What are two inhibitors of GABA tranporters
Nipecotic Acid
Tiagabine
What are the difference in effects between amphetamine and methamphetamine
Methamphetamine produces more exaggerated effects related to higher effective doses and greater propensity for addition
What are some effects of chronic methamphetamine use (6)
1) Drug-craving
2) Withdrawal-related depression
3) Rapid tooth decay
4) Degeneration of dopaminergic neurons
5) Weight loss
6) Psychosis
What is the MOA of amphetamine at DAT
Amp is a false substrate
Reduces DA uptake and causes reverse transport of DA
What are some additional actions of amphetamines (2)
Inhibits MAO
Competes with VMAT (depletes storage of DA in vesicles)
What is cocaine (2)
Na channel blocker
DAT, NET, SERT inhibitor
What are the effects of cocaine (3)
Simulate
Appetite suppressant
Topical anaesthetic
What is the MOA of cocaine
Competitive blocker of dopamine, noradrenaline and serotonin transport
