Methylxanthines and Nootropics Flashcards
What are the top tea drinking nations?
Turkey
Ireland
UK
What are the top chocolate consuming nations?
Switzerland
Austria
Ireland
What are the top coffee drinking nations?
Finland
Norway
Iceland
How are new chemicals identified and characterized by pharmacological activity?
Extraction
Purification
Predictions
Characterization
What series of experiments should psychoactive chemicals pass?
Animal behavior
Physiological measures
Biochemical assays
What does caffeine metabolize into?
Theophylline, theobromine, paraxanthine
What do chlorogenic acids do?
Induce (phase 2 transferases) liver enzymes
What does dihydrocaffeic acid do?
It is anti-inflammatory with vascular benefits as it promotes NO production
What are kahweol and cafestol?
Diterpenes
What do kahweol and cafestol do?
Increase phase 2 enzymes, induce anti-stress genes, and elevates cholesterol
What are the most common anti-oxidant sources?
Coffee and tea
What is aminophylline?
Anti-asthmatic; treatment of COPD
What is IBMX
A bronchodilator
What is pentoxifylline used to treat?
Vascular disease and is fibrinolytic
What does propentofylline do?
It is neuroprotective
What are the medical indications for caffeine?
Respiratory stimulation in premature infants
Asthma = bronchodilator
Migraines = reduces cranial blood flow
What is the second more commonly prescribed NICU drug?
Caffeine
What is the most commonly consumed psychoactive substance?
Caffeine
Absorption of caffeine?
Ingestion
Absorbed in the small intestine
How long does it take the effects of caffeine absorption to peak?
45 minutes
How is caffeine distributed?
Amphipathic
Rapid
Widely distributed
How is caffeine metabolized?
By liver CYP1A2 via demethylation
Limited or no first-pass
What does paraxanthine do?
Increases blood glycerol/fatty acids via lipolysis
What does theobromine do?
Dilates vessels, increases urine volume
What does theophylline do?
Inhibits PDE, increases [cAMP], relaxes smooth muscle
How is caffeine excreted?
In the kidneys
What are the cellular drug actions of methylxanthines?
Non-selective adenosine receptor antagonist
Non-selective phosphodiesterase antagonist
Also targets Ca release, GABA receptors
ARs and PDE are ubiquitous
Which adenosine receptors play primary roles in caffeine effects?
A1 and A2a
Where are A1 and A2a receptors located?
Pre and post synaptically
How do A1 receptors affect second messenger signaling?
Inhibits adenylyl cyclase, reduced cAMP
How do A2a receptors affect second messenger signaling?
Activates adenylyl cyclase increased cAMP
How do A1 receptors affect NT release?
Inhibition
How do A2a receptors affect NT release?
Activation
What are the effects of caffeine on A1 receptors?
Increased NT release
What are the effects of caffeine on A2 receptors?
Decreased NT release
Where are A1 receptors expressed?
Throughout including reward, hippocampus
Where are A2a receptors expressed?
In DA-rich regions and olfactory bulb, mostly on GABAergic neurons
What are receptor extensive pairs
Form at rest or to form a signaling complex
-A1-D1
-2 A2a + 2D2
-A1 + A2a
What are the psychological effects of caffeine?
Alertness, arousal, focus
Enhanced mood, confidence, sociability
High doses can cause anxiety
What are the cognitive effects of caffeine?
Reduced blood flow to brain
Sleep inhibited
What are the muscular effects of caffeine?
Increased skeletal muscle contraction
Increased endurance
What are the cardiovascular effects of caffeine?
Low dose = decreased heart rate
High dose = increased heart rate and BP
What are the respiratory effects of caffeine?
Increased respiratory rate
Dilated bronchi
What are the effects of caffeine on fat?
Increased fat mobilization, fatty acids, glycerol
What are the GI effects of caffeine?
Increased HCl secretion in the stomach
Increased metabolic rate
What are the renal effects of caffeine?
Increased urination
What are the reproductive effects of caffeine?
Relaxed uterine muscles
What are the general effects of caffeine?
Simulant
Milder than cocaine and meth
What happens to NE, Glu, and DA after caffeine consumption?
Increased released
What are long-term drinkers of caffeine less likely to experience?
Elevated heart rates and BP
What can constriction in cranial vessels caused by caffeine treat?
Headaches
How is caffeine a diuretic?
Because it increases kidney blood flow, promotes urination, and prevents water/salt re-absorption by kidneys
How does caffeine affect heart rate, blood pressure, and endurance mechanisms?
Inhibits phosphodiesterase enzymes which metabolize cAMP, producing high cAMP levels
Results in relaxing of smooth muscle (vasodilation) but has a central vasoconstricting effect
Increases intracellular [Ca] by increases activation of Ca channels
Thought to increase work capacity of muscle
What is the reinforcing mechanism of caffeine?
Good dopamine release in the NAc due to blocking pre-synaptic A1 on DA-ergic VTA to NAc neurons
Pre-synaptic A1 signal via Gi/o
Increases Glu release in the NAc
How does caffeine facilitate wakefulness?
By disrupting adenosine signaling
How does adenosine normally trigger sleep?
Extracellular adenosine increases during waking until a point is reached that triggers sleep
How does adenosine come about?
Through the metabolism of ATP in neurons
What does stimulation of A2a receptors by adenosine in the hypothalamus do?
Triggers GABA release which inhibits arousal systems
How does caffeine affect adenosine binding?
Prevents adenosine binding to A2a receptors and interrupts the process which prevents GABA release, prevents arousal systems which leads to wakefulness
What is the relationship between coffee intake and Parkinson’s?
Strong inverse relationship
Might decrease risk of disease
Which polymorphism of CYP1A2 confers fast metabolism of caffeine?
*1A
At least 2 copies
Which polymorphism of CYP1A2 confers slow metabolism of caffeine?
*1F
At least one copy
What do slow metabolizers of caffeine show?
Increased dose-dependent risk
How does caffeine tolerance develop?
Fast
Tolerance to cardiovascular, respiratory, sleep effects, but not on the effects on mood
What are the symptoms of caffeine withdrawal?
Headache, fatigue, decreased energy, irritability, thirst
How fast does dependence develop?
Very quickly
What are the long-term health effects of caffeine?
Osteoporosis
Increased risk of panic attacks due to stimulant effects
Anti-depressant due to regulating synaptic neurotransmitter levels
What is a nootropic?
Cognitive enhancer
Does caffeine improve memory?
Yes
Acute doses increased BDNF and TrkB activation in the hippocampus
BDNF is linked to LTP
Remember objects better if learning while on caffeine
What are the top soft drink consuming countries?
Argentina
USA
Chile
What is taurine?
Found in monster, red bull
Anxiolytic due to glycine receptor activation and increased IPSPs
What are examples of other nootropics?
L-theanine
Herbs (Ginkgo, ginseng, Bacopa)
Nicotine
Ritalin (benzylpiperidine)
Amphetamines
Benzhydryl sulfinyls (-afinil family)
