Pschyostimulants

Question 1

Background

Answer 1

Class of psychoactive substances that increase the CNS activity
Inc. legal substances, prescribed medication and drugs of abuse
Why take them?? Alertness, energy, social disinhibition, pleasure

Question 2

Amphetamines

Answer 2

Class of synthetic psychoactive drugs derived from the alkaloid ephedrine
Ephedrine = alkaloid extracted from the plant Epehdra
Precursor for all synthetic amphetamines
Amphetamines share structural similarities w dopamine + noradrenaline

Question 3

MoA- competitive re-ruptake of amphetamines

Answer 3

Amphetamines are competitively re-uptaken into the pre-synaptic nerve terminal via the dopamine transporter (DAT) + the noradrenaline transporter (NET)
= less dopamine (DA) and noradrenaline (NA) being taken up into the pre-synaptic nerve terminal as A is competitively taken up in its place
Once inside the pre-synaptic nerve terminal, A is taken up into vesicles by VMAT1/2
A accumulates in these vesicles and disrupts the pH gradient needed for the transporters to function
VMAT1/2 becomes non-functional and DA/NA accumulate in the cytosol
A activates intracellular TAAR1 receptors- can lead to the reversal of DAT + NET, and the removal of DAT + NET from the plasma membrane
= increase in DA + NA in the synaptic cleft, resulting in increased DA + NA post-synaptic receptor activation

Question 4

MDMA- what is it?

Answer 4

MDMA = 3,4-Methylenedioxymethamphetamine
Synthetic psychoactive drug w psychostimulant + psychoactive properties
Shares structural similarities w DA + NA

Question 5

MDMA MoA- competitive re-uptake

Answer 5

MDMA is competitively re-uptaken up into the pre-synaptic nerve terminal via DAT + NET + serotonin transporter (SERT)
= less DA, NA + 5-HT being taken up into the pre-synaptic nerve terminal as MDMA is competitively taken up in its place
MDMA inhibits VMAT1/2
= DA, NA + 5-HT accumulate in the cytosol
MDMA activates intracellular TAAR1 receptors- can lead to the reversal of DAT, NET + SERT, and the removal of DAT, NET + SERT from the plasma membrane
= Increase in DA, NA + 5-HT in the synaptic cleft
= increased DA, NA + 5-HT post-synaptic receptor activation

Question 6

Cocaine- what is it?

Answer 6

Cocaine = alkaloid derived from the coca plant
Typically extracted in a paste and converted into a hydrochloride or sulfate salt
Salt can be prepared in a variety of diff ways to facilitate intake
Shares minor structural similarities w DA + NA

Question 7

Cocaine- MoA

Answer 7

MOA- non-competitive block
Cocaine is a non-competitive blocker of DAT + NAT
= less DA + NA are taken up into the pre-synaptic terminal
This leads to an increase in DA + NA in the synaptic cleft
= increased DA + NA post-synaptic receptor activation

Question 8

Khat/cathinone- what is it?

Answer 8

Khat = naturally-occurring plant that contains the alkaloid cathinone
Shares structural similarities w DA + NA
Cathinone compounds have recently been synthesised
Synthetic cathinones are chemically related to khat, but the effects of these drugs are heightened

Question 9

Khat: MoA

Answer 9

MOA- non-competitive block
Cathinones are non-competitive blockers of DAT + NET
= less DA +NA are taken up into the pre-synaptic terminal
= increase in DA + NA in the synaptic cleft
= increased DA + NA post-synaptic receptor activation

Question 10

Dopaminergic effects of psychostimulants

Answer 10

Amphetamines, MDMA, cocaine and khat all increase DA
DA = neurotransmitter in the PNS + CNS
Metabotropic (GPCRs) have 5 subtypes:
D1, D5 = couple of Gs proteins to stimulate adenylate cyclase
D2, D3, D4 = couple to Gi/o and inhibit adenylate cyclase
DA metabolised by monoamine oxidase (MAO)
DA re-uptaken into pre-synaptic terminal by a selective DA active transporter- DAT