amphetamines Flashcards
where are amphetamines derived from
chinese medicine herb ma huang (5000 years)
who is credited with synthesizing AMPH and when
lazar edeleanu, 1885
what are the effects of L-amphetamine
raises BP
opens nasal passages
causes headache
what are the effects of D-amphetamine
same as L-amphetamine
also enhances mood and energy
how does meth have increased potency and brain effects?
lipid solubility
what are the 2 ways of synthesizing meth
pseudoephedrine (hydroiodic acid + red phosphorus) - nagai
from phenyl acetone (lamarck or reductive amination)
how are AMPHs absorbed
smoking injection snorting ingesting
what is the smokeable version of meth & what is its half life
ice, 12 hours
how is ice absorbed & what is its bioavailability
GI tract 70-100
what metabolizes meth and AMPH
cyp2d6 in liver
what are the stimulants that AMPH is metabolized into
4HA and NE
what does 4-HA act
inhibit MAO and activate TAAR and stimulate NE
what is the enzyme that reduces rate and what is the demographic distribution of its effect
cyp2d6*10
10% caucasions, 75% east asians
how is AMPH/METH distributed?
brain lungs liver kidney spleen
what is the onset of AMPH/METH
30-120 min
what is the half life of METH
12+ hr half- life 10-20 hours
what is the half life of AMPH?
11 hr half life, 3-12 hr
how is METH/AMPH excreted?
kidney sweat saliva
what are the acute affects of AMPHs
euphoria, energy, aggression, grandiositty, decreased appetite
what causes the sympathiomimetic effects of AMPH?
NE
what causes the delusional parasitosis and perceptual disturbances of AMPHs?
5HT
what causes the strange locomotor activity of AMPHs
increased DA
which area of the brain controls selection of action of movement?
basal ganglia
what is punding`
at high doses of AMPH, repetitive meaningless behaviors
does AMPH require DA-ergic neuron firing
nah
what brings meth into nerve terminals
DAT or diffusion
what pumps meth into storage vesicles
VMAT
what does AMPH increase the availability of
DA, NE, 5HT
where does AMPH cause a DA surge
NAc, basal ganglia
what are the 3 main mechanisms of AMPH
blocks reuptake & reverses transporter
increase release into synapse
inhibit MAO
what reverses DAT
AMPH-TAAR complex and DA build-up
how does AMPH mechanism differ from cocaine?
smaller structure allows transporter to complete transport
intracellular GPCR TAAR
how does TAAR work?
acttivates phosphorylation depdent signaling that targets DAT
how can AMPH cause poisoning
contaminants
how does tolerance form for AMPH
DA, 5HT and NE depletion via displacement of these NTs from terminals
inhibition of tyrosine hydroxylase
reducing DAT function
how long does tolerance last for AMPH
days or weeks
what is the withdrawal for AMPH
physical and psychological
craving, depression, lethargy msucle pain, abnormal sleeping patterns, anhedonia
how does dependence occur for AMPH
reduced cell surface expression for DA and NE
where does TAAR activation occur with respect to reduced transporter expression
upsteeam
what can reduce the effect of AMPH
TAAR1 agonists
what kind of mice are more sensitive to DA activation
TTAR1 knockout mice
what are the 3 main physical long term consequences `
weight loss, skin breakdown, sores/picking
how does AMPH cause decreased saliva?
alpha 1 on vessels , alpha2 on salivary glands
how does AMPH cause brain damage?
excitotoxicity stresses neurons and induces cell death
what happens as cells recover from MAO inhibition
elevated DA metabolism results in reactive species formation which damages cell membrane proteins and mito
how is damage measured
reduced volume/ reduced neurons
where is the most significant loss of neurons in the brain
cingulate gyrus
which losses correlate to word-recall issues in long-term METH users
hippocampal
how much more likely are METH users to develop Parkinsons
75%
