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Herbs > 5. Acetylcholine receptors > Flashcards

5. Acetylcholine receptors Flashcards

1
Q

how to sleep better (3)

A
  • sleep consistency: brain loves routine
  • red light therapy (we used to wake up at night to tend the fire)
  • weighted blankets (increase sleep in children with ADHD)
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2
Q

nervous system separates into 2, then each separates into 2 again, then one of them separates into 2

A

NERVOUS SYSTEM:
1) Central nervous system
a) brain
b) spinal cord (connects brain and peripheral nervous system)
2) peripheral nervous system: carries messages to and from CNS
a) somatic nervous system: controls voluntary muscles and transmits sensory info to CNS
b) autonomic nervous system: controls involuntary body functions
i) SNS: arouses body to expend energy (fight or flight)
ii) PSNS: calms body to conserve and maintain energy (rest and digest)

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3
Q

does PSNS or SNS:
- constrict pupil
- dilate pupil
- constricts airways
- dilates airways
- stimulates bile release
- stimulate sweat secretion
- increase rate of glycogen to glucose
- stimulates digestive
- decrease digestive
- relax uterus
- vaginal contraction
- relaxes bladder
increases urinary output
- stimulates adrenaline prod

A
  • constrict pupil: PSNS
  • dilate pupil: SNS
  • constricts airways PSNS
  • dilates airways SNS
  • stimulates bile release PSNS
  • stimulate sweat secretion SNS
  • increase rate of glycogen to glucose SNS
  • stimulates digestive PSNS
  • decrease digestive SNS
  • relax uterus PSNS
  • vaginal contraction SNS
  • relaxes bladder SNS
  • increases urinary output PSNS
  • stimulates adrenaline prod SNS
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4
Q

SNS vs PSNS

FUNCTION
OVERALL EFFECT (cata or anabolic)
ORGANS AND GLANDS IT ACTIVATES
HORMONES AND SUBSTANCES IT INCREASES
BODY FUNCTIONS IT ACTIVATES
PSYCHOLOGICAL QUALITIES
FACTORS THAT ACTIVATE SYSTEM

A

SNS:
FUNCTION: defend body against attack
OVERALL EFFECT: catabolic
ORGANS AND GLANDS IT ACTIVATES: brain, muscles, insulin pancreas, thyroid, adrenal glands
HORMONES AND SUBSTANCES IT INCREASES: insulin, cortisol and thyroid hormones
BODY FUNCTIONS IT ACTIVATES: raises BP and blood sugar, increase heat prod
PSYCHOLOGICAL QUALITIES: fear, guilt, sadness, anger, willfulness, aggressiveness
FACTORS THAT ACTIVATE SYSTEM: stress, fear, anger, worry, excessive thinking, too much exercise

PSNS:
FUNCTION: healing, regeneration and nourishing body
OVERALL EFFECT: anabolic
ORGANS AND GLANDS IT ACTIVATES: liver, kidneys, enzyme pancreas, spleen, stomach, small intestine, colon
HORMONES AND SUBSTANCES IT INCREASES: parathyroid hormone, pancreatic enzymes, bile, digestive enzymes
BODY FUNCTIONS IT ACTIVATES: digestion, elimination, immune system
PSYCHOLOGICAL QUALITIES: calmness, contentment, relaxation
FACTORS THAT ACTIVATE SYSTEM: rest, sleep, meditation, relaxation therapies, feelings of being loved

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5
Q

which types of neurons and neurotransmitter for somatic nervous system, PSNS and SNS?

A

somatic:
- cholinergic neurons –> acetylcholine

PSNS: cholinergic neurons for both pre and post-ganglionic
- acetylcholine for both!

SNS:
- cholinergic and ACh for pre-ganglionic
- adrenergic and norepinephrine for post-ganglionic OR epinephrine via bloodstream

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6
Q

what are the 5 categories of neurotransmitters? + examples ish

A
  1. acetylcholine (PSNS and pre-ganglionic SNS)
  2. amino acids: glutamate, GABA, glycine
  3. Monoamines: indolamines (serotonin) and catecholamines (dopamine, NE, E)
  4. purines: adenosine
  5. peptides: opioid
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7
Q

Acetylcholine
- found where (4)
- use to treat (2)
- 2 types of receptors!

A
  • found in motor neuron (muscles), brain, SNS (pre-ganglionic) and PSNS (both ganglionic and terminal)
  • used to treat Alzheimer’s disease and dementia

1) ionotropic: nicotinic receptors
2) metabotropic: muscarinic receptors

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8
Q

whats the difference between nicotinic receptors and muscarinic receptors?
- slow or fast response?

A

NICOTINIC
- ionotropic –> ion channels!
- multimers, has 2 domains: extracellular (Ach binds) and transmembrane (where ions pass through)
- mediate rapid effect!

MUSCARINIC:
- metabotropic –>activation of G proteins
- extracellular: neurotransmitter binding site vs intracellular: G-protein binding set
- slower response

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9
Q

TOBACCO (monograph):
- SCIENTIFIC NAME:
- PART USED:
- MODE OF ADMINISTRATION:
- BIOACTIVE COMPOUND:
- COMPOUND CLASS:
- USES: (5)

A
  • SCIENTIFIC NAME: nicotiana tabacum (tobacco)
  • PART USED: leaves
  • MODE OF ADMINISTRATION: insufflation (blow it in someone’s nose) OR inhalation (smoke it)
  • BIOACTIVE COMPOUND: nicotine
  • COMPOUND CLASS: alkaloid
    USES:
  • entheogenic (makes you feel high)
  • stimulant/sedative
  • antispasmodic
  • antinausea
  • expectorant: makes you spit
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10
Q

Nicotine
- acts as what?
- addictive?
- causes overflow of what?
- activates SNS or PSNS? –> stimulates release of what neurotransmitter?

A
  • acts as receptor agonist! (acts as Ach) –> at a7 nicotinic acetylcholine receptors (a7nAChR)
    *a7 is the most abundant nAChR in the CNS
  • HIGHLY addictive –> directly stimulates ACh receptors on dopamine containing neurons
  • causes overflow of dopamine in reward centers of brain –> dopamine = root of all addictions –> affects limbic system
  • activates SNS –> stimulates release of epinephrine
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11
Q

explains 4 steps of ACh synapse ish

A
  1. Action potential arrives in pre-synaptic neuron
  2. vesicle fuses with plasma membrane
  3. neurotransmitter/ACh from vesicle released into synaptic cleft
  4. Ach binds to nicotinic acetylcholine receptors (ionotropic) (nAChR) –> AP continues to next neuron
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12
Q

what are the 3 ways to get rid of neurotransmitters? (ie Ach)

A
  1. enzymatic degradation: acetylcholinesterase breaks down ACh
  2. reuptake by presynaptic neuron
  3. diffusion away from synapse
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13
Q
  • what is a PAM?
  • is nicotine a PAM?
  • potential therapeutic uses nAChR (6)
A
  • positive allosteric modulators –> bind at other sites on receptor
  • nicotine is NOT a PAM –> nicotine is an ACh agonist! (binds where ACh usually binds)
  • cognitive disorders
  • schizophrenia
  • Alzheimer’s disease
  • epilepsy
  • inflammation
  • pain
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14
Q
  • where are a7nAChRs abundantly expressed in the brain? (5)
  • dysfunction of a7nAChR associated with what? (5)
A
  • regions underlying cognition, memory, sensory processing, attention and reward
  • psychiatric and neurological diseases: schizophrenia, Alzheimer’s disease, ADHD, addiction, Parkinson’s disease
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15
Q

how can nicotine/n7AChR induce addiction? in which 4 pathways + 1 area of the brain ish?

A
  • nicotine on n7AChR –> can innervate dopaminergic neurons (Dopamine!) = addiction!
  • in ventral tegmental area (in brainstem) (where nicotine binds, where addiction happens) +
  • mesocortical
  • nigrostriatal pathway
  • tubero-infundibular pathway
  • mesolimbic pathway
    (aka cortical-limbic pathway)
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16
Q

explain mechanisms of what happens fo a7nAChR when you’re addicted to nicotine (4 steps)

A
  1. craving: no nicotine in system, receptor is closed
  2. smoke cigarette: in present of nicotine (ACh agonist), receptor opens and lets signal through –> leads to release of dopamine = reward
  3. cigarette just finished: receptor is desensitized and does not respond to more nicotine –> receptor is closed
  4. long term smoking increases craving: more receptors are formed with long-term exposure to nicotine: brain increases receptors bc R are stimulated not by brain (but by cigarette) –> so takes more nicotine to reach same stimulus
17
Q

TOBACCO
- curing and aging of tobacco leaves generates what?
- starch is converted to _______ –> which _________ proteins –> ___________ into (A)?
- inhalation of (A) is a major contributor to (2)
- manufacturers use ________ to do 3 things in tobacco industry

A
  • generates carcinogenic tobacco-specific nitrosamines (TSNAs)
  • starch is converted to sugar, which glycates proteins –> oxidizes into advanced glycation endproductions (AGEs)
  • inhalation of AGEs is a major contributor to atherosclerosis and cancer
  • use additives to enhance flavour, reduce harshness, and increase addictiveness (ammonia)
18
Q

Definitions:
INSUFFLATION:
EXPECTORANT:
STIMULANT:
DEPRESSANT:
ENTHEOGENIC:

A

INSUFFLATION: act of blowing something into a body cavity
EXPECTORANT: promotes secretion of sputum
STIMULANT: causing raised levels of physiological or nervous activity in body
DEPRESSANT: causing reduced functional or nervous activity
ENTHEOGENIC: drug that causes one to become inspired or to experience feelings of inspiration, often in a religious or spiritual manner

19
Q

Fly agaric (monograph)
- SCIENTIFIC NAME:
- PART USED:
- MODE OF ADMINISTRATION:
- BIOACTIVE COMPOUND:
- COMPOUND CLASS:
- USES: (4)

A
  • SCIENTIFIC NAME: amanita muscaria
  • PART USED: entire mushroom
  • MODE OF ADMINISTRATION: ingestion
  • BIOACTIVE COMPOUND: muscarine
  • COMPOUND CLASS: alkaloid
    USES:
  • entheogenic
  • hallucinogen
  • antinausea
  • expectorant
20
Q

muscarine
- how much is found in amanita muscaria?
- acts as what?
- causes activation of what?
- why is it super toxic?
- can cause (2)
- used to treat (3)
- what is an antidote ish?

A
  • trace amounts!
  • mimics actions of ACh (ACh agonist) on muscarinic acetylcholine receptors (metabotropic receptors)
  • cause profound activation of PSNS.
  • not degraded by acetylcholinesterase, explaining its toxicity
  • can cause circulatory collapse and death
  • glaucoma (decrease pressure in eye), hirschprung disease (congenital megacolon), and dry mouth
  • treated with atropine! an antagonist of muscarinic receptors
21
Q

amanita poisoning:
- fatal dose?
- predictable symptoms?
- symptoms (a lot)

NOT ON EXAM

A

15 caps (no size mentioned)
- unpredictable: based on habitat and amount eaten

  • nausea, stomach aches, vomiting
  • exceessive salivation, loss of balance, twitching, trembling
  • dissociative effects similar to Z-drugs like ambien and lumesta (sleeping drugs)
  • changes in perception (depth and size)
  • euphoria, relaxation, hypnotic, sedative
22
Q

what is the main psychoactive compound in amanita muscarita?
- what is its pre-drug? –> cause what?
- compound acts as what?
- responsible for which effects of amanita poisoning?

A
  • muscimol! (not muscarine) and its pre-drug ibotenic acid –> cause of hallucinations and toxicity
  • muscimol is a potent selective GABA receptor agonist (GABA = relaxant, inhibitor)
  • responsible for drunkenness, sedative, euphoric, and dissociative effect + sedative, hypnotic, depressant and hallucinogenic psychoactivity
23
Q

ibotenic acid
- potent agonist of (2)
- responsible for which symptoms (3) associated with amanita ingestion
- how is it converted to the psychoactive compound of amanita?

A
  • potent agonist of N-methyl-D-aspartate (NMDA) and metabotropic glutamate receptors
  • nausea, stomach cramps, vomiting
  • undergoes decarboxylation in kidneys to generate muscimol (psychoactive compound)
24
Q

what are 3 main plants used in divination + their main compounds?

A
  1. angel’s trumpets
    - brugmansia spp.
    - tropane alkaloids: scopalamine, hyoscymine, atropine –> very potent!
  2. Jimson weed
    - datura stramonium
    - tropane alkaloids: scopalamine, hyoscymine, atropine
  3. morning glory
    - ipomoea tricolor
    - ergoline alkaloids: ergonovine, ergine
25
Q

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

A
  • SCIENTIFIC NAME: Datura stramonium
  • PART USED: seeds/leaves
  • MODE OF ADMINISTRATION: ingestion, smoked
  • BIOACTIVE COMPOUND: atropine, hyocyamine, scopalamine
  • COMPOUND CLASS: tropane alkaloids! (basket!)
  • USES: entheogenic + hallucinogenic
26
Q

tropane alkaloids
- what does they do?
- suppresses which NS?
- can cause (3)
- 3 examples
- medicinal use? for each type (don’t need to know)

A
  • anti-cholinergic!: inhibits transmission of neurotransmitter acetylcholine! antagonists!
  • suppressed PSNS
  • can cause pronounced amnesia, bizarre behaviour and inability to distinguish reality from fantasy

ATROPINE:
- eye drops used to dilate pupils (inhibit PSNS to have SNS action)
- injections used in treatment of bradychardia
SCOPOLAMINE:
- used to treat motion sickness and postoperative nausea
HYOSCYAINE:
- provide symptomatic relief of spasms caused by peptic ulcers, IBS, diverticulitis, pancreatitis and colic

27
Q

which plant was thought to be Moly from Homer’s Odyssey?
- what is the bioactive compound?
- used to treat what?
- acts as what?

A

Snowdrop (galanthus nivalis)
- galantamine!
- used to treat Alzheimer’s disease
- acts as n acetylcholinesterase inhibiter –> counteracts effects of datura stramonium (Jimson weed) (tropane alkaloids = anticholinergic ) –> bc increase ACh in synaptic cleft!

28
Q

what is the method of action of galantamine?
- found in which plant

A

in snowdrop (galanthus nivalis)
1. galantamine is a potent positive allosteric modulator (PAM) ligand of nAChR –> it increases receptor’s response to ACh
2. galantamine inhibits acetylcholinesterase and increases concentration and action of ACh!

  • reverses effect of tropane alkaloids (which inhibit ACh)
29
Q
  1. ACh is made of (2)
  2. in synaptic cleft, how is ACh broken down?
  3. what happens to degradation products?
A
  1. made of choline and actyl-coA
  2. acetylcholinesterase breaks down ACh
  3. choline is transported back into axon terminal and is used to make more ACh
30
Q
  • how do you get anticholinergic toxidrome?
  • what are the symptoms of anticholinergic toxidrome?
A
  • competitive antagonism of acetylcholine at central and peripheral muscarinic receptors –> from too much tropane alkaloids
  • blind as a bat (dilates pupils)
  • mad as a hatter (confused)
  • red as a beet (flushed skin)
  • hot as a hare (can’t regulate heat well)
  • dry as a bone (dry mouth, urinary retention)
  • bowel and bladder lose their tone (absent bowel sounds, no peeing?)
  • and the heart runs alone (tachycardia)
    + shaking, grabbing invisible objects
31
Q

what are glycoalkaloids?
- bing strongly to what? causing what?
- mechanism of action? can lead to (4)
- examples?

A
  • natural pesticides found in high concentration in leaves, flowers and unripe fruit
  • bind strongly to cholesterol in cell membranes –> causing cells to leak or burst open
  • BLOCKS ENZYME ACETYLCHOLINESTERASE! –> can lead to paralysis, convulsions, respiratory arrest and death
  • sprouts and green spots in potatoes are dangerously high in glycoalkaloids

*intact glycoalkaloid is poorly absorbed from gut but causes gastrointestinal irritation –> the aglycone is absorbed and is believed to be responsible for observed nervous system signs

32
Q

chili pepper (MONOGRAPH)
- SCIENTIFIC NAME:
- PART USED:
- MODE OF ADMINISTRATION:
- BIOACTIVE COMPOUND:
- COMPOUND CLASS:
- USES:

A
  • SCIENTIFIC NAME: Capsicum annuum
  • PART USED: fruit
  • MODE OF ADMINISTRATION: ingestion
  • BIOACTIVE COMPOUND: capsaicin
  • COMPOUND CLASS: capsaicinoid (N-containing lipid)
  • USES: analgesic (pain relief), strong irritant, antiseptic, antirheumatic
33
Q

SUMMARY SLIDE:
Name:
1) ACh agonist on metabotropic receptor
2) ACh agonist on ionotropic receptors
3) ACh antagonist on muscarinic and nicotinic receptors
4) acetylcholinesterase inhibitor (2)

A

1) Muscarine
2) Nicotine (tobacco)
3) tropane alkaloids
4) galantamine (snowdrop) and glycoalkaloids (potato sprouts)

34
Q

which type of molecules increase PSNS activation = relax?
VS which type reduce PSNS activation?

A

Acetylcholine inhibitors (galantamine + solanaceous glycoalkaloids)
- PSNS increased activation! = relax
- bradychardia, bronchoconstriction, GI tract hypermobility, decreased intraocular pressure, increased salivation…

ACh antagonists (tropane alkaloids)
- PSNS reduced activation
- CNS depression: amnesia, fatigue, reduction in REM
- anti-parkinson drug, anti-alzheimer’s drug, antidepressent
- anticholinergic toxidrome
- true hallucinations

35
Q
  • act of blowing something into a body cavity
  • promotes secretion of sputum
  • causing raised levels of physiological or nervous activity in body
  • causing reduced functional or nervous activity
  • drug that causes one to become inspired or to experience feelings of inspiration, often in a religious or spiritual manner
A
  • insufflation
  • expectorant
  • stimulant
  • depressant
  • entheogenic

Herbs (12 decks)

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