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Herbs > 6-7: aa + Monoamine receptors > Flashcards

6-7: aa + Monoamine receptors Flashcards

1
Q

what are the 3 important amino acids?

A

glutamate
GABA (gamma amino-butyric acid)
glycine

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2
Q

glutamic acid decarboxylase converts glutamic acid to what?

A

to GABA!

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3
Q

GLUTAMATE:
- found where? excites (5)
- plays a critical role in (2)
- used to treat what?
- receptors are all __________ –> 2 main types we need to know?

A
  • found everywhere in CNS –> excites cerebral cortex, spinal cord, brain stem, hippocampus, cerebellum
  • plays a critical role in long-term potentiation (memory) and neuroplasticity (reforming brain pathways)
  • used to treat amyotrophic lateral sclerosis (ALS)
  • receptors are all EXCITATORY –> ionotropic: NMDA vs AMPA receptors
    (also kainate receptor (ionotropic) and metabotropis (group 1, 2, 3))
  • universal excitator!!!
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4
Q

what are the differences btw AMPA and NMDA receptors?
- for which neurotransmitter?

A
  • for glutamate!
    AMPA:
  • Na+ and K+ influx only
  • responds to weak stimulation
    NMDA:
  • needs 2 ligands (glutamate + glycine)
  • needs electrostatic repulsion to unplug Mg++ block –> IMPORTANT!
    *weak stimulation can unlodge Mg –> then Ca2+ can enter –> lots of post-synaptic effect (ie can recruit more AMPA)
  • Ca++ influx along with Na+ and K+
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5
Q
  • what is excitotoxicity?
  • which type of receptors are responsible for excitotoxicity and cell death?
  • results from excessive stimulation of what? (2)
  • BUT these receptors can also contribute to 2 positive things
  • conditions linked to excitotoxicity (6)
A
  • trauma!! (associated with glutamate)
  • extrasynaptic NMDA receptors!
  • results from excessive stimulation of NMDA and AMPA receptors (core memory)
  • synaptic NMDA receptors contribute to health and longevity of cells
  • stroke, traumatic brain injury, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer’s disease, spinal injuries
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6
Q

which compound can attenuate NMDA-induced excitotoxicity?

A

Curcumin! protects neurons from glutamate induced excitotoxicity

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7
Q

TURMERIC (monograph)
- SCIENTIFIC NAME:
- PART USED:
- MODE OF ADMINISTRATION:
- BIOACTIVE COMPOUND:
- COMPOUND CLASS:
- USES:

A
  • SCIENTIFIC NAME: Curcuma longa
  • PART USED: rhizome (root)
  • MODE OF ADMINISTRATION: oral (fresh or boiled, ground)
  • BIOACTIVE COMPOUND: curcumin
  • COMPOUND CLASS: curcuminoid (phenolic compound)
  • USES: anti-inflammatory + antioxidant + boosts BNDF (brain derived neurotropic factor) + Anti-Alzheimer’s (can cross BBB)
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8
Q

GABA = universal what?
- stands for what?
- found where? (2 ish)
- inhibits or activate which parts of nervous system?
- used to treat (3 main categories ish)
- receptors?

A
  • gamma-aminobutyric acid = universal inhibitor!
  • found everywhere in CNS + in interneurons
  • inhibits cerebral cortex, spinal cord, brainstem, hippocampus, cerebellum, basal ganglia
  • anxiety and rehab for drug use (too little GABA = generalized anxiety) + inhibits motor, sensory, cognitive neurons + sedation, muscular/cardiovascular relaxation, inhibits pain and reflexes
  • ALL inhibitory! have both ionotropic and metabotropic GABA (A vs B) receptors
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9
Q

GABA receptors have a lot of what? give examples
- plants that affect GABA will be covered in which lecture?

A

have a lot of PAMs!
- benzos –> benzodiazepine (sedative, hypnotic, anxiolytic, anticonvulsant, muscle relaxant)
- barbs –> barbituates (CNS depressant, hypnotic, anxiolytic, anticonvulsant, potentially addictive)

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10
Q

GLYCINE
- found where?
- inhibits or activates what?
- used to treat what?
- receptor?

A
  • found only in spinal cord!
  • inhibits spinal cord interneurons
  • used to treat spasticity
  • only ionotropic Cl- channel receptors! no metabotropic
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11
Q

Strychnine
- acts as what? –> result?
- occurs in which part of which scientific plant?
- used to make what?

A
  • act as selective competitive ANTAGONIST to block the inhibitory effects of glycine at the glycine receptors
  • occurs in seeds of strychnos nux-vomica (Loganiaceae)
  • used to make poison arrows
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12
Q

STRYCHNINE TREE: (monograph)
- SCIENTIFIC NAME:
- PART USED:
- MODE OF ADMINISTRATION:
- BIOACTIVE COMPOUND:
- COMPOUND CLASS:
- USES:

A
  • SCIENTIFIC NAME: strychnos nux-vomica
  • PART USED: seeds
  • MODE OF ADMINISTRATION: inhgestion, inhalation, injection (arrow piercing)
  • BIOACTIVE COMPOUND: strychnine
  • COMPOUND CLASS: alkaloid
  • USES: poison, convulsant
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13
Q

Strychnine poisoning
- strychnine is a what?
- also an agonist/antagonist of which receptors?
- affects what?
- poisoning results in what? –> eventual what?

A
  • glycine receptor antagonist
  • antagonist of ACh receptors –> inhibits relaxation
  • affects motor nerve fibers (muscles) in the spinal cord –> which control muscle contraction
  • poisoning results in muscular convulsions
  • eventual death through asphyxia (choking)
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14
Q
  • what are the 4 main monoamines?
  • why are they called monoamines?
  • 2 categories –> examples, synthesized using what? degraded using what?
A
  • serotonin (happiness)
  • dopamine (satisfaction, addiction)
  • norepinephrine
  • epinephrine
    *because 1 nitrogen!
    1. catecholamines:
  • dopamine, epinephrine (adrenaline)
  • synthesized from tyrosine
  • degraded intracellularly by monoamine oxidase (MAO)
    2. indolamines:
  • serotonin
  • synthesized from tryptophan
  • degraded intracellularly by MAO
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15
Q

AYAHUASCA (monograph)
- SCIENTIFIC NAME:
- PART USED:
- MODE OF ADMINISTRATION:
- BIOACTIVE COMPOUND:
- COMPOUND CLASS:
- USES:

A
  • SCIENTIFIC NAME: banisteriopsis caapi
  • PART USED: stems and bark
  • MODE OF ADMINISTRATION: decoction (drink it)
  • BIOACTIVE COMPOUND: Harmine
  • COMPOUND CLASS: Alkaloid
  • USES: entheogenic + monoamine oxide inhibitor!
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16
Q

what are the 2 “ingredients” of ayahuasca/to get high? give examples of plants

A
  1. MonoAmine Oxidase INHIBITOR!
    - ie ayahuasca (banisteriopsis caapi)
  2. Dimethyltryptamine (DMT) containing plants
    - chacruna (psychotria viridis), chagropanga (diplopterys cabrerana), jurema preta (mimosa tenuiflora)
    - DMT is naturally endogenously produced
    OR
  3. non-DMT containing plants (used instead of psychotria)
    - water willow (justicia pectoralis), angel’s trumpets (brugmansia), aztec tobacco (nicotania rustica)
17
Q
  • what is the most abundant b-carboline (or harmala alkaloid) in Banisteriopsis caapi?
  • what does it do? (2)
  • used as what before arrival of what
A
  • Harmine!
  • inhibits breakdown of monoamie transmitters (serotonin and dopamine) and hormones (melatonin, epinephrine, NE)
  • as MAO inhibitors, harmine can replenish levels of serotonin and dopamine
  • MAOis were used as anti-depressants before arrival of selective serotonin receptor inhibitors (SSRIs) in 1987
18
Q

what is the only known drug to induce proliferation of alpha and beta cells of pancreas of adults?
- how does that drug do so?
- benefit for who?

A
  • harmine! (in ayahuasca)
  • inhibits DYRK1A enzyme pathway –> plays a role in suppressing and regulating cell proliferation
  • has been found to increase beta-cell mass (produces insulin) in people with type 1 and type 2 diabetes. research as a possible treatment is ongoing
19
Q

DMT
- derivative of what?
- responsible for what?
- can we produce DMT endogenously?
- can it be eaten?

A

N,N dimethyltryptamine
- tryptamine!
- responsible for hallucinogenic properties of ayahuasca (Yagé)
- we may produce DMT endogenously –> our own body’s psychedelic! –> through meditation or by dying…
- DMT CANNOT be eaten –> MAO in the stomach and GI lining metabolize it before entering bloodstream –> it can be prepared as a powdered snuff (have someone blow it into your brain/nose cavity

20
Q

DMT acts as what? how do we know that?
- also acts as what?
- can accumulate where?

A
  • acts as agonist of 5-HT receptor (serotonin receptors!)
  • serotonin receptors have shown desensitization with repeated exposure to DMT (only 5-HT2C though, not 5-HT2A)
  • also acts as agonist of 5-HT1A and increases subjective effects of DMT, suggesting a buffering effect on hallucinogenic effects of 5HT2 receptors
  • DMT accumulates in cerebral cortex, caudate, putamen and amygdala (limbic/emotions center!)
21
Q

serotonin (scientific way of writing ish?)
- found where? (a lot of places)
- used to treat (2)
- receptors?

A

5-HT
- brain and brainstem: pineal gland, raphe nuclei in pons, limbic function –> emotions, mood, hunger, sex, instincts, temp, sex
- used to treat depression and sleep regulation
- ionotropic (excitory) and metabotropic (excitatory and inhibitor)

22
Q

SEROTONIN
- most found where in body? where it helps control what?
- produced by which cells?
- what can influence its production and the availability of which aa?
- important axis? thus?

A
  • most found in gut! where it helps control bowel movements
  • produced by enterochromaffin (EC) cells lining the digestive tract
  • healthy gut bacteria can produce short-chain FA like butyrate that can influence the production of serotonin in enterochromaffin cells –> can also alter availability of tryptophan
  • BRAIN-GUT AXIS! more nerves in gut than in spinal cord! link btw depression and IBS is strong –> enteric nervous system!
23
Q

what does serotonin act as in the
BRAIN? –> regulates (7)
vs GUT? –> regulates (5)

A

BRAIN: acts as an inhibitory neurotransmitter that regulates
- mood, fear, anxiety
- feelings of relaxation, mental focus, clarity of thought
- learning ability
GUT: acts as a hormonal messenger that regulates
- satiety
- food cravings
- digestion
- nutrient absorption
- peristalsis

24
Q

what happens when you have low serotonin (5) vs normal (2) vs high (2)

A

LOW:
- depression
- anxiety
- pain sensitivity
- sleep disturbances
- fatigue
NORMAL:
- happiness and relaxation
HIGH
- medical emergency –> death
- causes: SRIs and OTC supplements –> not natural

25
Q

ERGOT (monograph)
- SCIENTIFIC NAME:
- PART USED:
- MODE OF ADMINISTRATION:
- BIOACTIVE COMPOUND:
- COMPOUND CLASS:
- USES:

A
  • SCIENTIFIC NAME: claviceps purpurea
  • PART USED: sclerotium
  • MODE OF ADMINISTRATION: ingestion
  • BIOACTIVE COMPOUND: esgotamine
  • COMPOUND CLASS: ergoline alkaloid
  • USES: hallucinogenic + psychedelic –> psychotic (changes behavior)
26
Q

what are the 2 pathways of ergotism?

A
  1. serotonergic stimulation of CNS
    - ergotamine is an agonist of the 5-HT (serotonin) receptors (5HT1 and 5HT2)
    - characterized by muscle spasms, fever and hallucinations. victims may appear dazed, unable to speak, become manic or have other forms of paralysis or tremors, and suffer from hallucinations and other distorted perceptions
  2. VASOCONSTRICTION of vascular system
    - violent burning, absent peripheral pulses and shooting pain of the poorly vascularized distal organs (fingers and toes) –> can lead to gangrene and loss of limbs
27
Q

what is st-Anthony’s fire? what caused it?
- that compound is a what?

A

medieval Europe plague that caused convulsions and gangrene
- caused by ergot fungus which produced ergot alkaloids!
- monoamine hallucinogens!

28
Q

Morning glory (monograph)
- SCIENTIFIC NAME:
- PART USED:
- MODE OF ADMINISTRATION:
- BIOACTIVE COMPOUND:
- COMPOUND CLASS:
- USES:

A
  • SCIENTIFIC NAME: Ipomoea tricolor
  • PART USED: seeds
  • MODE OF ADMINISTRATION: ingestion
  • BIOACTIVE COMPOUND: ergine
  • COMPOUND CLASS: ergoline alkaloid
  • USES: hallucinogenic, psychedelic (but no vasoconstriction like ergot)
29
Q

what is LSD-25 derived from?

A

from ergot! (claviceps purpurea)

30
Q

ERGOT ALKALOIDS
- 2 main pathways ish. explain
- inhibits what?
- used in medicine to treat what?

A
  1. SEROTOGENIC: similar structure to serotonin, dopamine and E. can bind to several receptors, acting as an agonist
  2. VASOCONSTRICTION: stimulates a-adrenergic receptors (increases blood pressure) –> this is what caused dry gangrene in St-Anthony’s dire
    - inhibits reuptake of NE
    - used in med to treat migraines
31
Q

what are 6 ways to raise serotonin levels naturally?

A
  • food (CHO increase Tryptophan transport across BBB)
  • exercise: releases tryptophan in blood + decrease levels of other aa
  • bright light! (outside or sun lamp)
  • mood and mindset: think positive
  • massage: hug, intimacy, human touch
  • probiotics: improves gut health (serotonin released in gut!)
32
Q

St John’s Wort (monograph):
- SCIENTIFIC NAME:
- PART USED:
- MODE OF ADMINISTRATION:
- BIOACTIVE COMPOUND:
- COMPOUND CLASS:
- USES:

A
  • SCIENTIFIC NAME: Hypericum perforatum
  • PART USED: Flower and buds
  • MODE OF ADMINISTRATION: tea or tincture
  • BIOACTIVE COMPOUND: hyperforin and hypericin
  • COMPOUND CLASS: phloroglucinol
  • USES: antidepressent
33
Q

St John’s Wort
- what is the bioactive compound? similar activity to what? but with better ____________
- used to treat what? effectiveness?
- clinical research?

A
  • Hyperforin! displays similar activity to other selective serotonin reuptake inhibitors (SSRIs) and with better tolerance
  • 2008 cochrane review of 29 clinical trials that it was superior to placebo in patients with major depression, as effective as standard antidepressants and had fewer side-effects
  • clinical research results are mixed. might not be effective for everyone. some may experience side effects (digestive issue, sleep issues, fatigue, skin rashes, photosensitivity)
34
Q

St-John’s Wort
- induces which enzymes?
- what does that do? (2 + long list)

A
  • induces the cytochrome P450 enzymes CYP3A4 and CYP1A2
  • this increases metabolism of certain drugs! –> decreased plasma concentration + decreased clinical effects!
  • drugs that St John’s Wort can affect include: contraceptives, immunosuppressants, benzodiazepines, beta-blockers, calcium channel blockers, statins
35
Q

RECAP
- what is the universal excitator? receptors? plant example? what does it do?
- main inhibitor in spinal cord? where in body? receptors? what plant? what does it do?

A

GLUTAMATE = excitator
- ionotropic: AMPA and NMDA
- curcumin: attenuates excitotoxicity

GLYCINE = main inhibitor in spinal chord
- ionotropic Cl- channels
- strychnine: glycine receptor antagonist

36
Q

SEROTONIN:
- all # receptors except _____ are which type?
- 3 categories ish of compounds that are related to it

A

all 7 receptors except 5-HT3 are metabotropic
1. harmine (in Ayahuasca): inhibits monoamine oxidase and breakdown of serotonin
2. ergotamine and ergine (ergot): 5-HT receptor agonist
3. hyperforin and hypericin: inhibits reuptake of serotonin. may have MAOi activity

*all 3 are antidepressants and make you happy (?)

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