Psychostimulants Flashcards
What are psychostimulants? (2)
A class of psychoactive substances that increase the activity of the central nervous system (CNS).
include legal substances (e.g., caffeine, nicotine), prescribed medication (e.g., Ritalin) and drugs of abuse (e.g., MDMA)
WHY DO PEOPLE TAKE PSYCHOSTIMULANTS? (5)
Multi-fold (for example):
* Alertness
* Energy
* Social disinhibition
* Pleasure
The Misuse of Drugs Act 1971
Drugs are divided into three
classes in accordance with the
harmfulness attributed to a drug
when it is misused
The Misuse of Drugs Regulations 2001
Drugs are divided into five schedules each specifying requirements governing
activities concerning a particular drug (e.g. production, supply, possession, prescribing)
Amphetamines- intro (4)
A class of synthetic psychoactive drugs derived from the alkaloid ephedrine.
- Ephedrine = alkaloid extracted from the plant Ephedra – used to treat specificconditions (e.g., airway obstruction as a bronchodilator)
- Ephedrine a precursor for all synthetic amphetamines
- Amphetamines share structural similarities with dopamine and noradrenaline
Amphetamine MoA (6)
1) Taken up into vesicles by
VMAT/2
2) Increase in DA + NA in the synaptic cleft = leading to increased DA and NA post-synaptic
receptor activation
3) Amphetamines activate intracellular TAAR1receptors, which can lead to the reversal of
DAT +NET and the removal of DAT + NET from the plasma membrane
4) Amphetamines accumulate in vesicles = disrupt the pH gradient required for transporters to function – VMAT1/2 become
non-functional and DA/NA accumulate in cytosol
5) competitively re-uptaken up into the pre-synaptic nerve terminal via
the dopamine transporter (DAT) +
noradrenaline transporter (NET)
6) = This leads to less dopamine (DA) and noradrenaline (NA) being taken up into the pre-synaptic nerve terminal as amphetamine is competitively taken up in its
place
MDMA- intro (5)
(3,4-Methylenedioxymethamphetamine) is a synthetic psychoactive drug
- MDMA 1st synthesised in 1912 by the pharmaceutical company Merck in attempts to develop a vasoconstrictor
- MDMA was subsequently used in the 1970s by some underground
psychiatrists within psychotherapy - However, today, MDMA is best known as a recreational drug of abuse with psychostimulant and psychedelic properties
*MDMA shares structural similarities with dopamine and
noradrenaline
MDMA-MoA (5)
- MDMA is competitively re-uptaken up into the pre-synaptic nerve terminal via the dopamine transporter (DAT) and the
noradrenaline transporter (NET) and the serotonin transporter (SERT) - This leads to less DA, NA and serotonin (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 and 5-HT accumulate in the cytosol
- MDMA activates intracellular
TAAR1 receptors, which can lead to
the reversal of DAT, NET and SERT
and the removal of DAT, NET and
SERT from the plasma membrane - Increase in DA, NA and 5-HT in
the synaptic cleft, leading to
increased DA, NA and 5-HT
post-synaptic receptor
activation
Cocaine-intro (4)
Alkaloid derived from the coca plant (Erythroxylun coca).
- Coca leaves used for thousands of years (e.g., South America) for stimulant effects – in the West, cocaine widely used toward latter half of the 19th century
in coca wines, cigarettes, and medicines - Cocaine shares minor structural similarities with dopamine and
noradrenaline - Cocaine typically extracted in a paste and converted into a hydrochloride or sulfate salt – salt can be prepared in a variety of ways to facilitate intake
(e.g., coke, crack)
Cocaine-MoA (3)
- Cocaine is a non-competitive blockerof the dopamine transporter (DAT) and the noradrenaline transporter (NET)
- This means less DA and NA
are taken up into the pre-
synaptic terminal - This leads to an increase in DA
and NA in the synaptic cleft,
leading to increased DA and NA
post-synaptic receptor
activation
Khat-Intro (5)
A naturally-occurring plant that contains the alkaloid cathinone.
- Khat usage dates to at least the 11th century and is a social mainstay in several countries (e.g., Yemen) – leaves chewed with effects similar (but lesser) to
amphetamines - Cathinone compounds have more recently been synthesised
(e.g., mephedrone) - Synthetic cathinones are chemically related to khat –however, the effects of these drugs are heightened Mephedrone
- Cathinone shares structural similarities with dopamine and noradrenaline
Khat-MoA (3)
- Cathinones are non-competitive
blockers of the dopamine transporter (DAT) and the noradrenaline transporter (NET) - This means less DA and NA
are taken up into the pre-
synaptic terminal - This leads to an increase in DA
and NA in the synaptic cleft,
leading to increased DA and NA
post-synaptic receptor activation
Dopaminergic effects of psychostimulants
Increases DA:
Amphetamines
MDMA
Cocaine
Khat
Dopamine Definition
A neurotransmitter in the peripheral nervous system (PNS) and in the central nervous
system (CNS) that can have both inhibit AND excitatory effects
Recap of dopaminergic signalling
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