Corso Stuff

  1. Biogenic Amines

    1. dopamine, norepinephrine, 5-HT, ACh, histamine, melatonin

      1. all of the basic ones

  2. amino acids (AAs)

    1. glutamate, glycine, GABA

      1. ALL START WITH G

  3. purigenic

    1. adenosine, ATP

      1. ALL START WITH A

  4. peptide

    1. encephalins, endorphins

      1. START WITH E

  5. retrograde transmitters

    1. nitric oxide, endocannabinoids

      1. WEIRD ONES

    2. endocannabinoids regulate glutamate and GABA release

    3. I THINK HE’LL ASK ABOUT ENDOCANNABINOID BEING A RETROGRADE TRANSMITTER

  1. STRUCTURES

    1. acetylcholine: NO RINGS, 7 C’s

    2. dopamine: 1 ring, one amine

    3. norepinephrine: 1 ring, one amine, one hydroxyl

    4. epinephrine: 1 ring, one amine, one hydroxyl, additional methyl

      1. SO REMEMBER: DA —> NE —> EPI

        1. each step adds an additional group

    5. 5-HT: 2 rings, one amine

    6. melatonin: 2 rings, carboxylic acid added on

      1. SO REMEMBER: 5-HT —> melatonin

        1. so the step is an additional group

    7. histamine: 1 ring with 2 N’s in it

      1. I ALSO think of histamine looking like a chiller melatonin

    8. glutamate: 5 C’s

    9. GABA: 4 C’s

      1. 4 LETTERS —> 4 C’S

    10. glycine: 2 C’s

      1. serine —> glycine

        1. REMOVES A CARBON

    11. adenosine: looks like a purine

    12. endocannabinoids: arachidonic acid derivatives, 20 C’s

    13. ATP: 3 phosphate groups

      1. don’t overthink it, you know what it looks like

  1. SEROTONIN

    1. structure: 2 rings, one amine

    2. found: raphe

    3. synthesis: tryptophan —> 5-HTP —> 5-HT

      1. precursors:

        1. tryptophan

        2. 5-hydroxytryptophan

    4. degradation: serotonin broken down by MAO-A —> 5-hydroxyindoleacetaldehyde —> 5-hydroxyindole acetic acid

      1. drug targets: MAOIs

        1. inhibits degradation of serotonin (depression and anxiety)

    5. VMAT2: inhibited by reserpine

    6. receptors:

      1. inward sodium channels

        1. 5HT3

      2. trimeric Gi —> decr. cAMP, decr. PKA

        1. 5HT1

      3. trimeric Gq —> DAG, IP3, Calcium, PKC

        1. 5HT2

      4. trimeric Gs —> cAMP, PKA

    7. 5HT3 inhibitors are used for nausea caused by chemo

  1. MELATONIN

    1. structure: 2 rings, one amine, carboxylic acid

    2. found: pineal gland

    3. synthesis: tryptophan —> 5-HTP —> 5-HT —> N-acetyl serotonin —> melatonin

      1. precursors:

        1. tryptophan

        2. 5-HTP

        3. 5-HT

        4. N-acetyl serotonin

  1. HISTAMINE

    1. structure: 1 ring with 2 N’s

    2. found: hypothalamus

      1. THINK H GOES WITH H

    3. function: alertness

    4. synthesis: histidine (histidine decarboxylase) —> histamine

      1. precursor: histidine

    5. degradation: histamine (SAM) —> methylhistamine (MAO-B) —> methylimidazole acetic acid

    6. VMAT2: inhibited by reserpine

    7. receptors:

      1. trimeric Gs —> cAMP, PKA

        1. H2

      2. trimeric Gq —> DAG, IP3, Calcium, PKC

        1. H1

    8. H1: EXCITATORY: DAG, IP3, calcium, PKC

    9. H2: EXCITATORY: incr. cAMP

    10. H3, 4: INHIBITORY

  1. AcetylCholine

    1. structure: NO RINGS, 7 C’s

    2. found: nucleus basalis/basal ganglia

      1. pre-ganglionic autonomic cells

    3. Alzheimer’s: causes depletion

      1. treatment: acetylcholinesterase inhibitors

    4. synthesis: acetyl coA + choline

      1. enzyme: choline acetyltransferase

    5. degradation: acetylcholinesterase (results in acetyl coA and choline)

      1. drug target for myasthenia gravis and alzheimer’s

    6. botulinum toxin blocks release

    7. receptors:

      1. inward sodium channels

        1. N1, N2 (5 subunits) (nicotinic)

      2. trimeric Gi —> decr. cAMP, decr. PKA

        1. m2 (muscarinic)

      3. trimeric Gq —> DAG, IP3, Calcium, PKC

        1. m1 (muscarinic)

    8. nicotinic receptors

      1. FAST

      2. N1: muscles

      3. N2: neurons

    9. muscarinic receptors

      1. SLOWER

      2. odd numbers: 1, 3, 5: EXCITATORY Gq

      3. even numbers: 2, 4: INHIBITORY Gi

    10. myasthenia gravis:

      1. serum antibodies against N1 receptors

        1. typical: alpha 1 subunit

        2. acquired slow channel: epsilon subunit

        3. neonatal: gamma subunit

      2. ACETYL CHOLINESTERASE INHIBITORS

    11. LEMS (lambert-eaton myasthenic syndrome)

      1. immune disorder against voltage gated calcium channelscc

  1. DOPAMINE

    1. structure: 1 ring, 1 amine

    2. found: substantia nigra

      1. flow: substantia nigra —> striatum

    3. too little: Parkinson’s

      1. side effect of D2 antagonists: Parkinsonian tremors

    4. too much: schizophrenia, hallucinations

    5. synthesis: phenylalanine —> L-tyrosine (hydroxylation) —> L-dopa (decarboxylation) —> dopamine

      1. precursors:

        1. phenylalanine

        2. tyrosine

    6. degradation: MAO-B and COMT

      1. drug targets: MAOIs and COMTIs

        1. prevent degradation —> increase dopamine levels (Parkinson’s)

      2. metabolites:

        1. DOPAL

        2. DOPET

        3. DOPAC

        4. 3-Me-DOPET

        5. 3-Me-DOPAL

        6. 3-MT

        7. HVA

    7. Parkinson’s treatment: L-dopa + carbidopa

      1. L-dopa can cross the BBB, dopamine can NOT

      2. carbidopa can NOT cross the BBB, prevents L-dopa from converting in the periphery —> minimizes ADRs

    8. VMAT2: inhibited by reserpine

    9. receptors:

      1. trimeric Gs —> cAMP, PKA

        1. D1

      2. trimeric Gi —> decr. cAMP, decr. PKA

        1. D2

    10. D1 and D5: EXCITATORY

      1. think as the ones on the ends

    11. D2, D3, and D4: INHIBITORY

      1. the middle ones

  1. NOREPINEPHRINE

    1. structure: 1 ring, one amine, one hydroxyl

    2. found: locus ceruleus

      1. post-ganglionic sympathetic cells

    3. synthesis: phenylalanine —> L-tyrosine (hydroxylation) —> L-dopa (decarboxylation) —> dopamine (hydroxylation) —> norepinephrine

      1. precursors:

        1. phenylalanine

        2. tyrosine

        3. dopamine

    4. degradation: MAO and COMT

      1. drug targets: MAOIs and COMTIs

        1. prevent degradation —> increase dopamine levels (DEPRESSION)

    5. VMAT2: inhibited by reserpine

    6. receptors:

      1. trimeric Gs —> cAMP, PKA

        1. beta 1,2,3

      2. trimeric Gi —> decr. cAMP, decr. PKA

        1. alpha 2

      3. trimeric Gq —> DAG, IP3, Calcium, PKC

        1. alpha 1

    7. alpha 1: EXCITATORY: DAG, IP3, calcium, PKC

    8. alpha 2: INHIBITORY

    9. beta 1,2,3: EXCITATORY: cAMP, PKA

  1. EPINEPHRINE

    1. structure: 1 ring, one amine, one hydroxyl, additional methyl

    2. found: adrenal gland

    3. synthesis: phenylalanine —> L-tyrosine (hydroxylation) —> L-dopa (decarboxylation) —> dopamine (hydroxylation) —> norepinephrine (SAM) —> epinephrine

      1. precursors:

        1. phenylalanine

        2. tyrosine

        3. dopamine

        4. norepinephrine

    4. degradation: MAO and COMT

      1. drug targets: MAOIs and COMTIs

        1. prevent degradation —> increase dopamine levels (DEPRESSION)

    5. receptors:

      1. trimeric Gs —> cAMP, PKA

        1. beta 1,2,3

      2. trimeric Gi —> decr. cAMP, decr. PKA

        1. alpha 2

      3. trimeric Gq —> DAG, IP3, Calcium, PKC

        1. alpha 1

  1. GLUTAMATE

    1. structure: 5 C's

    2. most abundant NT in the brain and spinal cord

    3. receptors:

      1. inward sodium channels

        1. AMPA

          1. fast sodium

        2. kainate

          1. fast sodium

        3. NMDA (glutamate/glycine) —> memory!!!

          1. slow

      2. trimeric Gi —> decr. cAMP, decr. PKA

        1. mGluR2

      3. trimeric Gq —> DAG, IP3, Calcium, PKC

        1. mGluR1

    4. NMDA, AMPA, kainate: EXCITATORY: inward sodium channels

    5. mGluR1: EXCITATORY: DAG, IP3, calcium, PKC

    6. mGluR2: INHIBITORY

    7. transporter: VGLUT

    8. drugs that block glutamate release: riluzole, lamotrigine, topiramate, levetiracetam, gabapentin, pregabalin

      1. decreases amount of glutamate in synapse —> treats overactivity —> anticonvulsants, epilepsy, anxiety, etc.

    9. drugs that enhance reuptake: riluzole, tianeptine

      1. decreases amount of glutamate in synapse

    10. glutamate receptor agonist (AMPA/Kainate): domoic acid

      1. toxin in contaminated shellfish (from algae)

    11. glutamate receptor antagonist (AMPA): perampanel, halothane

      1. treat seizures / anesthetic

    12. glutamate receptor inhibitor (NMDA): memantine

      1. treat’s alzheimer’s

  1. GABA

    1. structure: 4 C’s

      1. THINK 4 LETTERS, 4 C’S

    2. most common INHIBITORY NT in brain

    3. synthesis: glutamate —> GABA (removes a CO2)

    4. degradation: converted back to glutamate

    5. receptors:

      1. inward chloride channels (inhibitory)

        1. GABA-A, C

      2. outward potassium (inhibitory)

        1. GABA-B

    6. benzos bind to the GABA site and open the chloride channel —> alleves anxiety

  1. GLYCINE

    1. structure: 2 C’s

    2. most common INHIBITORY NT in the spinal cord

    3. synthesis: serine —> glycine (removes carbon)

      1. THF removes the carbon

    4. receptors:

      1. inward sodium channels

        1. NMDA (glutamate/glycine)

      2. inward chloride channels (inhibitory)

        1. glycine

  1. ATP

    1. structure: 3 phosphate groups

    2. “co-transmitter”: common to find purigenics copackaged with ACh or catecholamines

    3. receptors:

      1. inward sodium channels

        1. P2X1-7

          1. found both pre and postsynaptic

  1. ENKEPHALINS

    1. structure: peptide

    2. receptors:

      1. outward potassium channels

        1. mu

        2. delta

  1. ENDORPHINS

    1. structure:

    2. receptors:

      1. outward potassium channels

        1. mu

  1. ENDOCANNABINOIDS

    1. structure: arachidonic acid derivatives, 20 C’s

    2. receptors:

      1. trimeric Gi —> decr. cAMP, decr. PKA

        1. CB1, 2

*note: nerve growth factor is an insulin-like receptor

SO IN TERMS OF THE RECEPTORS

    good rule of thumb is that the even numbers are inhibitory Gi (m2, D2, alpha 2, mGluR2)

        the main exception is serotonin, where 5HT1 is inhibitory (think of it like there’s another number in there so it’s opposite)

        other exceptions are things like beta 1-3 and N 1-2 which all do the same thing

        other exception is H1 and H2, both are excitatory but H1 is Gq, H2 is Gs (2 looks like s)