Lecture 4 from a college level neuropharmacology course taught in the spring 2012 semester by Brian J. Piper, Ph.D. (psy391@gmail.com) at Willamette University. Includes hypericum, melatonin, ginsing, serotonin

1. Neuropharmacology &
Behavior:
Herbal Drugs
Brian J. Piper, Ph.D.

2. Goals
• Tryptophan
• Melatonin
• Ginseng
• Hypericum

3. DSHEA of 1994
• Dietary Supplement Health & Education
Act: natural product ≠ drug
• Purity not regulated
• Efficacy not necessary
• Post-distribution safety

4. Advertising Gray Zone
Forbidden Permitted
Depression mood swings
Alzheimer’s cognitive improvement
Diabetes control blood sugar
Anxiety irritability

5. Some Organic Chemistry
• Enzyme- proteins that increases the rate of a chemical
reaction without themselves undergoing any change, -ase (Bettelheim &
March, 1991)
Enzyme
Substrate ----> Product
• Functional Groups: a combination of elements, includes
Nitrogen (N), Oxygen (O), Hydrogen (H), or Carbon (C)
– Hydroxyl: OH
– Carboxyl: COOH
– Amino: contains N

6. Tryptophan (C H N O ) 11 12 2 2
• Essential amino acid
• Dietary sources: milk, turkey, peanuts, fish
• Uses: antidepressant
insomnia,
anxiety
See also: http://en.wikipedia.org/wiki/Tryptophan

7. 5-HTP (5-Hydroxytryptophan)

8. 2.1
1
Melatonin
2
3
4
5

9. Circadian Rhythm of Melatonin
a
b

10. Ginseng
• renshen: man root
• Pharmacodynamics: ?
• Pharmacokinetics: ?
• Promoted uses: fatigue, stress, high blood
pressure, dementia, cancer, athletic performance,
and hot flashes.
See also: http://en.wikipedia.org/wiki/Ginseng

11. Anxiety in mice? Elevated Plus Maze
Ag. Dest = distilled water
Carr M.N. et al. (2006) European J Pharmacology, 531, 160-165.

12. Drug Comparisons
• Potency: amount of • Efficacy: how well a
drug to produce a drug produces a
response response
• (A= morphine, B=aspirin)

13. Hypericum perforatum
• St. John’s wort
• Hypericin, Hyperforin,
others
• “Side effect”:
photosensitivity

14. 6.0
“Definitive” study?
• Scientific literature Sertaline= Zoloft, a serotonin reuptake inhibitor
includes many
conflicting reports
about the
antidepressant effects
of hypericum
– Safety: better than
standard
antidepressants
– Efficacy: useful for
moderate and severe Hypericum Depression Trial Study Group (2002).
depression? JAMA, 287, 1807-1814.

15. Hypericum safety

16. Drug Interactions
• Drug metabolism is regulated by a family of enzymes in
the liver (CYPs)
• CYP2D6
– #: gene family (18)
– Letter: subfamily (43)
– #: Gene
• One drug can interfere with the metabolism of another
Enzyme
– Normal: Substrate ---------> Product
Enzyme
– Activation: Substrate ---------> Product
– Inhibition: SubstrateEnzyme Product
--------->
See also: http://en.wikipedia.org/wiki/Cytochrome_P450

17. 2.0
Example: Grapefruit juice

18. CYP3A4
• Substrates: largest of all CYP’s
• Hyperforin increases activity
• This can decrease plasma levels of other
drugs including:
– SSRI’s: e.g. fluoxetine
– Benzodiazepines: e.g. valium
– Testosterone
– Estradiol
See also: http://en.wikipedia.org/wiki/CYP3A4

19. Ephedra
– from Ma Huang
(herbal tea)
– isolated in 1920’s
– bronchodilator for
asthma
– pseudoephedrine is an
isomer of ephedrine
– structure similar to
epinephrine
Epinephrine
OH
CH CH NH CH 3
CH 3
Ephedrine

20. Drug Comparison
Synthetic Herbal
History 100 1000
# Few Many
Research Common Uncommon
Safety Varied Varied
2:35-50:40
http://videocast.nih.gov/summary.asp?Live=3573