neuropharmacology: herbal drugs
DESCRIPTION
Lecture 4 from a college level neuropharmacology course taught in the spring 2012 semester by Brian J. Piper, Ph.D. ([email protected]) at Willamette University. Includes hypericum, melatonin, ginsing, serotoninTRANSCRIPT
Neuropharmacology & Behavior:
Herbal Drugs
Brian J. Piper, Ph.D.
Goals
• Tryptophan
• Melatonin
• Ginseng
• Hypericum
DSHEA of 1994
• Dietary Supplement Health & Education Act: natural product ≠ drug
• Purity not regulated
• Efficacy not necessary
• Post-distribution safety
Advertising Gray Zone
Forbidden Permitted
Depression mood swings
Alzheimer’s cognitive improvement
Diabetes control blood sugar
Anxiety irritability
Some Organic Chemistry
• Enzyme- proteins that increases the rate of a chemical reaction without themselves undergoing any change, -ase (Bettelheim & March, 1991)
• Functional Groups: a combination of elements, includes Nitrogen (N), Oxygen (O), Hydrogen (H), or Carbon (C)
– Hydroxyl: OH– Carboxyl: COOH– Amino: contains N
Substrate ----> ProductEnzyme
Tryptophan (C11H12N2O2)
• Essential amino acid
• Dietary sources: milk, turkey, peanuts, fish• Uses: antidepressant
insomnia,
anxiety
See also: http://en.wikipedia.org/wiki/Tryptophan
5-HTP (5-Hydroxytryptophan)
Melatonin 1
2
3
4
5
2.1
Circadian Rhythm of Melatonin
a
b
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
Anxiety in mice? Elevated Plus Maze
Carr M.N. et al. (2006) European J Pharmacology, 531, 160-165.
Ag. Dest = distilled water
Drug Comparisons• Potency: amount of
drug to produce a response
• Efficacy: how well a drug produces a response
• (A= morphine, B=aspirin)
Hypericum perforatum
• St. John’s wort• Hypericin, Hyperforin,
others• “Side effect”:
photosensitivity
“Definitive” study?
• Scientific literature includes many conflicting reports about the antidepressant effects of hypericum– Safety: better than
standard antidepressants
– Efficacy: useful for moderate and severe depression?
Hypericum Depression Trial Study Group (2002). JAMA, 287, 1807-1814.
Sertaline= Zoloft, a serotonin reuptake inhibitor
6.0
Hypericum safety
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 – Normal: Substrate ---------> Product
– Activation: Substrate ---------> Product– Inhibition: Substrate ---------> Product
See also: http://en.wikipedia.org/wiki/Cytochrome_P450
Enzyme
Enzyme
Enzyme
Example: Grapefruit juice2.0
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
Ephedra
– from Ma Huang (herbal tea)
– isolated in 1920’s– bronchodilator for
asthma– pseudoephedrine is an
isomer of ephedrine– structure similar to
epinephrine
CH NHCH CH3
CH3
OH
Ephedrine
Epinephrine
Drug Comparison
Synthetic Herbal
History 100 1000
# Few Many
Research Common Uncommon
Safety Varied Varied
http://videocast.nih.gov/summary.asp?Live=3573 2:35-50:40