Methylxanthines

Question 1

coffee

Answer 1

botanical preparation
infusion of complex chemicals from a plant fruit

Question 2

identification of new chemicals

Answer 2

extraction
purification
predictions
characterization

Question 3

experiments for psychoactive chemicals

Answer 3

animal behaviour
physiological measures
biochemical assays

Question 4

primary actives in caffeine

Answer 4

methylxanthines

Question 5

methylxanthines

Answer 5

heterocyclic alkaloids
purine base nucleus

= 2 rings with N
2 carboxyls

Question 6

chlorogenic acids

Answer 6

induce liver enzymes
(phase II transferases like GST)

Question 7

dihydrocaffeic acid

Answer 7

anti-inflammatory with vascular benefits
promotes NO production

Question 8

Kahweol and cafestol

Answer 8

diterpenes
increase phase II enzymes
induce anti stress genes
elevate cholesterol

Question 9

most common anti-oxidant sources

Answer 9

coffee and tea

Question 10

synthetic xanthines

Answer 10

aminophylline
IBMX
pentoxifylline
propentofylline

Question 11

medical indications for caffeine

Answer 11

respiratory stimulation in premature infants
2nd most commonly rxed NICU drug

asthma → bronchodilator
migraines → reduces cranial blood flow

Question 12

respiratory stimulation

Answer 12

PDE4 inhibition increases [cAMP] in rhythmogenic preBotC complex

Question 13

most commonly consumed psychoactive substance

Answer 13

caffeine

Question 14

absorption

Answer 14

ingestion
small intestine
45 min to peak

Question 15

distribution

Answer 15

amphipathic (small molecule)
rapid
widely distributed

Question 16

metabolism

Answer 16

no first pass
CYP1A2 → demethylation
caffeine → theophylline, theobromine, paraxanthine

Question 17

paraxanthine

Answer 17

84%
increases blood glycerol/fatty acids via lipolysis

Question 18

theobromine

Answer 18

12%
dilates vessels
increases urine volume

Question 19

theophylline

Answer 19

4%
inhibits PDE → increases [cAMP]
relaxes smooth muscle

Question 20

excretion

Answer 20

kidney

Question 21

cellular drug actions

Answer 21

non-selective adenosine receptor antagonists
non-selective phophodiesterase (PDE) antagonists
[receptors are expressed broadly in the body]

targets Ca2+ release, GABA receptors

Question 22

adenosine receptors

Answer 22

A1, A2a, A2b, A3
presynaptic receptors - limit NT release

receptors form extensive pairs
A1-D1, 2 A2a + 2 D2, A1 + A2

Question 23

AR signaling

Answer 23

antagonist of all 3 types
effects primarily by A1 and A2a

Question 24

A1

Answer 24

pre- and post-synaptic
Gi = inhibits AC, reduced cAMP
inhibition of NT release
caffeine increases NT release
expressed in reward circuit, hippocampus

Question 25

A2

Answer 25

pre- and post-synaptic
Gs = activates AC, increased cAMP
activation of NT release
caffeine decreases NT release
expressed in DA-rich regions + olfactory bulb; GABA-ergic neurons

Question 26

acute effects of caffeine

Answer 26

general stimulant effects
similar to cocaine, AMPH - milder

Question 27

physiological mechanisms

Answer 27

increase NE, glu, DA release
constriction of cranial vessels - treat headaches
diuretic → increases kidney blood flow, promotes micturition, prevents reabsorption of water/salt by kidneys

Question 28

heart effects

Answer 28

high cAMP levels → relaxation of smooth muscle (vasodilation) but central vasoconstriction

biphasic effect on hr
low dose = ↓ hr
high dose = ↑ hr, bp

Question 29

endurance mechanisms

Answer 29

increases intracellular concentration of calcium by increasing activation of calcium channels
= increase work capacity of muscles

Question 30

reinforcing mechanisms

Answer 30

dopamine release in NAc (2x baseline)
due to blocking pre-synaptic A1 on DAergic VTA→NAc neurons
presynaptic A1 signal via Gi/o
increases glu release in NAc

Question 31

wakefulness

Answer 31

metabolism of ATP in neurons → adenosine
levels increase during waking

stimulation of A2a receptors in hypothalamus → triggers GABA release = inhibits arousal systems

Question 32

caffeine facilitation of wakefulness

Answer 32

disrupts adenosine signaling
prevents adenosine binding to A2a receptors → prevents GABA release = prevents inhibition of arousal systems = wakefulness

Question 33

parkinson’s disease

Answer 33

strong inverse relationship between caffeine and parkinson’s

Question 34

CYP1A2 polymorphisms

Answer 34

*1A = fast metabolic rate (need two copies)
*1F = slow metabolic rate (at least one copy)

slow metabolizers show increased dose dependent risk of heart attack

Question 35

tolerance

Answer 35

develops quickly
to elevated heart rate/bp (CV + resp effects) and sleep
not to mood effects

Question 36

withdrawal

Answer 36

headache, fatigue, decreased energy, irritability, thirst

Question 37

dependence

Answer 37

develops quickly
mild

Question 38

long term risks

Answer 38

osteoporosis
increased risk of panic attacks - stimulant effects

Question 39

osteoporosis

Answer 39

due to increased calcium elimination and reduced dietary Ca2+ absorption

Question 40

anti-depressants

Answer 40

adenosine receptor antagonists
due to regulating synaptic NT levels

Question 41

use during pregnancy

Answer 41

effects on fetus are inconclusive

Question 42

nootropic

Answer 42

cognitive enhancers

Question 43

caffeine - memory

Answer 43

positive effect on learning and memory
acute doses increase BDNF and TrkB activation in hippocampus
BDNF - linked to LTP

Question 44

taurine

Answer 44

in energy drinks
anxiolytic - glycine receptor activation and increased IPSPs

Question 45

nootropic examples

Answer 45

taurine
herbs
nicotine
AMPH - adderall
ritalin
-afinil family

Question 46

herbs

Answer 46

ginko biloba
panax ginseng
bacopa monnieri

Question 47

ritalin

Answer 47

benzylpiperidine

Question 48

-afinil family

Answer 48

modafinil
adrafinil
armodafinil