Opiates

1
Opiates

• History
• Chemical structure of opiates
• Bioavailability, Effects
• Receptors and Endogenous ligands
• Changes in cells mediated by opiates

2
Opiates

• Opium poppy, Papver somniferum

3
History

• Egyptians
• Greeks
• Islamic nations
• Sears and Roebuck!

4
Chemical Structures

• Agonists
• Morphine
• Codeine
• Heroin
• Antagonists
• Naloxone, Nalorphine
• Mixed agonist-antagonists
• Pentazocine (Talwin)
• Nalbuphine (Nubain), Buprenorphrine (Buprenex)

5
Bioavailability

• Morphine
• i.m., oral, i.v
• Heroin
• Snorting
• Skin popping (s.c.)
• Mainlining (i.v.)

6
Opiate Effects

• Low-moderate dose
• Pain relief
• Depression of respiration
• Pupil constriction
• Drowsiness
• Decreased sensitivity to environment
• Impaired concentration
• Dreamy sleep
• Limbic system functions
• Cough suppression
• Hypothalamic effects

7
Opiate Effects

• Higher doses (especially i.v. or inhaled)
• Elation/Euphoria
• Rapid administration
• Nausea, vomiting
• Body temperature, blood pressure fall
• Pupil constriction
• Extreme impairment of respiration

8
Opiate Effects

• Gastrointestinal Tract
• Treatment for diarrhea and dysentery
• Immodium!
• Side effects

9
Opioid Receptors

• Seven transmembrane domains
• Three subtypes
• Mu (m)
• Delta (d)
• Kappa (k)

10
Endogenous opioids

• Enkephalins and Endorphins
• Propeptides
• Prodynorphin
• Proopiomelanocortin (POMC)
• Stress
• Proenkephalin
• ?
• Endomorphins

11
Opiate Cellular Effects

• Inhibitory influence on cells
• Open K channels (postsynaptic)
• Close Ca channels (axoaxonic)
• Inhibit adenylyl cyclase (Gi g-protein)
• Somatodendritic autoreceptors