6 - Amphetamines Flashcards
ephedra sinica
what amphetamine was derived from
Ma huang
ephedra used as traditional Chinese medicine
Lazar Edelano
synthesized alpha-methylphenethylamine (amphetamine)
L-AMPH
- methyl in to the page
- raises bp
- opens passages
- causes headaches
D-AMPH
- methyl coming out of the page
- raises bp
- opens passages
- causes headaches
- elevates mood
- enhances energy
methamphetamine
increased lipid solubility therefore an increase in potency
making meth
- Nagai synthesis
- reductive amination
- Leuckart synthesis
Nagai synthesis
pseudoephedrine/ephedrine from OTC used to synthesize meth
reductive amination
add methylamine to phenylacetone
Leuckart synthesis
add methylamine to phenylacetone
structure of AMPH vs METH
meth has an extra methyl group than amph
ice
- smokeable meth with a half-life of 12 hrs
- 70-100% bioavailability
CYP2D6
liver enzyme that metabolized amph and meth
stimulants in AMPH and METH
- 4-hydroxyamphetamine (4-HA)
- norephedrine
4-HA
- activates trace amino acid receptor (TAAR)
- stimulates norephedrine release
- inihibits monoamine oxidase (MOA)
trace amino acid receptor (TAAR)
intracellular GPCR that reverses DAT activity
monoamine oxidase (MOA)
degrades NTs (5-HT, DA, NE)
acute effects
- euphoria
- energy
- decreased appetite
- sympathomimetic
- formication
- punding (meaningless behaviour)
AMPHs mechanism
- AMPH enters presynaptic cell and blocks DAT
- VMAT stores AMPH in vesicles
- AMPH blocks MOA by binding to it
- DA released into cytoplasm
- AMPH binds to TAAR which reverses DAT activity
AMPH vs cocaine mechanism
- AMPH is a smaller molecule, therefore it can fit in the transporter
- AMPH forms a complex with TAAR
adverse effects
- contaminants
- combining with other drugs to increase effect
tolerance
- DA. 5-HT, and NE displacement from terminals
- reduces DAT function
withdrawl
- cravings
- depression
- lethargy
- muscle pain
- emotional volatility
withdrawl period
can last up to 12 months due to permanent damage
dependance
reduced receptors for DA, NE
TAAR1 agonists
reduce the effects of AMPH
long-term consequences
- weight loss
- skin breaking
- sores
- tooth decay
- jaw grinding
- corrosive contaminants from ice
- reduced saliva production
- sensitization
- unprovoked aggression
- suicical/homicidal
- damage to DA, 5-HT, NE terminals
- stresses neurons (apoptosis) therefore brain damage
neuron loss in limbic system
- reduced volume indicated reduced neurons
- word recall issues observed due to loss in neurons in the hippocampus
- more susceptible to Parkinson’s due to loss of DA neurons
- reactive oxygen species production and stress due to calcium influx from nAChR activation
