Barker lecture 2

Question 1

Benzylisoquinolines

Answer 1

Noscapine (6%)
Papaverine (1%)

Question 2

Phenanthrenes

Answer 2

Morphine (10%)
Codeine (0.5%)
Thebaine (0.2%)

Question 3

Non-phenanthrenes

Answer 3

Tramadol
Meperidine
Fentanyl

Question 4

Human genome contains several genes encoding endogenous opioids

Answer 4

Peptides active endogenously

Large precursor proteins are cleaved into more opioid subtype selective peptides

Degree of redundancy

Question 5

Proopiomelanocortin (POMC)

Answer 5

B-endorphin–>mu opioid

Question 6

Preproenkephalin

Answer 6

Leu-enkephalin–> delta opioid

Met-enkephalin–>mu and delta

Question 7

Preprodynorphin

Answer 7

Dynorphin–>kappa opioid

Question 8

Nociceptin/Orphanin FQ

Question 9

G protein coupled receptor

Answer 9

Family A–peptide receptors

Gi/o coupled (inhibition of cAMP production)

Open GIRK(beta gamma) potassium channels–>hyperpolarized

Close calcium channels

Question 10

Mu

Answer 10

Morphine

Endogenous opioid=endorphin

Question 11

Kappa

Answer 11

ketocyclazocine

Endogenous opioid=dynorphin

Question 12

Delta

Answer 12

deferens–> where identified

endogenous opioid=enkephalin

Question 13

Opioid receptor for signal transduction

Answer 13

Presynaptic: inhibit calcium channel (Gi) decrease neurotransmitter release

Postsynaptic: activate GIRK channel (GBy) Efflux of K=hyperpolarization making it more negative and making it more difficult to reach

Question 14

Mu opioid receptor

Answer 14

Beta-endorphins (endogenous morphine)

Pro-opiomelanocortin
Component of runners high

Analgesia
Not as effective for chronic pain
Cancer pain, palliative, PCA

Sedation

Antitussive
Suppression of cough center in the medulla oblongata

Question 15

Opioid induced side effects are mostly on-target effects

Answer 15

Respiratory depression

Constipation

Itch

Addiction

Urinary retention: opioid-induced ADH release

N/V

Miosis: oculomotor nerve
not meperidine

Question 16

Kappa opioid receptor

Answer 16

Dynorphins natural ligand: preprodynorphin

Activation is dysphoric aversive

Potential use for treatment of addiction: reduce DA release

Counterbalance mu opioid receptor effects

Question 17

Delta opioid receptors

Answer 17

Enkephalins are natural ligand
Preproenkephalin

More dynamic expression

Role in hypoxia/ischemia/stroke
Hibernation release of enkephalin like opioid

Reduce anxiety
Reduce depression
Treat alcoholism
Relief hyperplasia;chronic pain

SE: SEIZURES
NO FDA APPROVED DELTA OPIOIDS

Question 18

Opioid site of action

Answer 18

nucleus accumbens

VTA

important for reward

almost all known substance uses have connections in these circuits

Question 19

Depressants can cause dopamine release just like stimulants

Answer 19

1. opioids bind mu receptor
2. Gi signaling inhibits neurotransmitter release
3. Less GABA to activate GABAa
4. Less inhibition of dopamine neuron activity
5. increase dopamine release
6. increased activation of dopamine receptors