1 bi 1 lecture 2 tuesday, march 28, 2006 revised 4/4/06 what is a drug? nicotinemorphine
TRANSCRIPT
![Page 1: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/1.jpg)
1
Bi 1 Lecture 2
Tuesday, March 28, 2006 Revised 4/4/06
What is a drug?
N
O
HO
HOCH3
morphine
N
CH3N
nicotine morphine
![Page 2: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/2.jpg)
2
drugnoun Pronunciation: 'dr&g Etymology: Middle English droggeDate: 14th century
1 a (obsolete) : a substance used in dyeing or chemical operations
b : a substance used as a medication or in the preparation of medication
c according to the Food, Drug, and Cosmetic Act
(1) : a substance recognized in an official pharmacopoeia or formulary
(2) : a substance intended for use in the diagnosis, cure, mitigation, treatment,
or prevention of disease
(3) : a substance other than food intended to affect the structure or function of
the body
(4) : a substance intended for use as a component of a medicine but not a
device or a component, part, or accessory of a device
2 : a commodity that is not salable or for which there is no demand--used in the phrase,
“drug on the market”
3 : something and often an illegal substance that causes addiction, habituation, or a
marked change in consciousness
![Page 3: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/3.jpg)
3
nicotine(Nestler Fig. 12-4)
N
CH3N
procaine(Nestler p. 50)
O
CH2
H2C
NH2
C O
NH3CH2C CH2CH3
Trivial names and Structural Formulas
botulinum toxin(Nestler p. 203, 323)
N
O
HO
HOCH3
morphine
morphine(Nestler Fig. 16-3)
![Page 4: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/4.jpg)
4
Today’s drugs exemplify the “Central Dogma of Drugs and the Brain”
Part 1: Drugs Activate (nicotine) and block (procaine) ion channels
Part 2: Drugs act on G protein pathways (morphine)
Part 3: Drugs activate genes (nicotine, morphine)
Part 4: Protein drugs may be the wave of the future for neuroscience diseases (botulinum toxin)
![Page 5: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/5.jpg)
5
Each moiety in a drug molecule has importance.Example: procaine
O
CH2
H2C
NH2
C O
HNH3CH2C CH2CH3
+
Charged amine: may bind to charged groups on the protein
Ester: hydrolyzed to terminate drug action
Aromatic: may bind to nonpolar groups on the protein
![Page 6: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/6.jpg)
6
nicotine procaine
N
CH3N
O
CH2
H2C
NH2
C O
NH3CH2C CH2CH3
botulinum toxin
Atomic-scale Structures
(Download to your computer;Then open with Swiss-prot pdb viewer)
N
O
HO
HOCH3
morphine
morphine
http://www.its.caltech.edu/~lester/Bi-1/nicotine.pdb
http://www.its.caltech.edu/~lester/Bi-1/procaine.pdb
http://www.its.caltech.edu/~lester/Bi-1/morphine.pdb
![Page 7: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/7.jpg)
7
nicotine procaine botulinum toxin
C13H20N2O2
236
Formulas and molecular weights (MW)
C10H14N2
162~150,000
morphine
C17H19N2O3
285
![Page 8: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/8.jpg)
8
nicotine procaine
Novocain®(Sanofi)
Trademark Names
botulinum toxin
BOTOX®(Allergan)
Marlboro®(Philip Morris);
Nicorette®(SmithKlineBeecham)
morphine
none
![Page 9: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/9.jpg)
9
nicotine
Type of CompoundType of Compound
morphine
(Alkaloids are a group of nitrogenous organic compounds
that have physiological effects on humans).
alkaloid
![Page 10: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/10.jpg)
10
procaine
Type of Compound
local anesthetic
(Synthetic organic compound)
Type of Compound
![Page 11: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/11.jpg)
11
botulinum toxin
Type of Compound
protein:
Chain of amino-acid residues joined by peptide bonds
Type of Compound
![Page 12: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/12.jpg)
12
nicotine
Routes into the Nervous System
Smoked;
chewed;
skin patch
procaine
Injected
botulinum toxin
Injected;
eaten
morphine
Injected;
suppository
![Page 13: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/13.jpg)
13
blood
mouth, stomach or lungs
RNH2 RNH3+
H+
RNH2 RNH3+
H+
often the active and predominant form
higher pH
Lipid barrier,e. g. membrane(s)
![Page 14: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/14.jpg)
14
Tobacco leaves are roughly 5% nicotine by weight.
http://www.philipmorrisusa.com/en/product_facts/ingredients/brand_by_brand_ingredients.asp
Other ingredients in Marlboro:
![Page 15: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/15.jpg)
16
nicotine: uptake through the lungs
N
CH3N
NH+
CH3N
H+
blood
lungs
N
CH3N
volatilized form
NH+
CH3N
H+
pKa = 8.0
pKa = 8.0
Marlboro 100's Filter Box RedAMMONIUM HYDROXIDE maintains neutral pH
Lipid barrier,e. g. membrane(s)
![Page 16: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/16.jpg)
17
Marlboro 100's Filter Hard Pack Red
TobaccoWater
Sugars (Sucrose, Invert Sugar, or Corn Syrup)
GlycerolPropylene Glycol
Cocoa & Cocoa ProductsLicorice Extract
Diammonium PhosphateAmmonium Hydroxide
Natural & Artificial Flavors
keeps the cigarette moist
flame retardant
keeps nicotine neutral
![Page 17: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/17.jpg)
18
Review of nicotine’s path from the lungs to the blood and the brain
N+H3C
N H
H+
vaporizedN
CH3N
Marlboro 100's Filter Box RedAMMONIUM HYDROXIDE removes H+
N
CH3N
H+ N+H3C
N H
bloodand brain
lungs
cells and membranes
![Page 18: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/18.jpg)
19
0
20
40
60
80
100
0 50 100 150
min
nM
Blood nicotine concentrations during and after a cigarette
smoking
![Page 19: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/19.jpg)
20
nicotine: uptake through the mouth and skin
http://nicorette.quit.com/
Nicorette Website
![Page 20: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/20.jpg)
21
levodopa, “L-dopa”zwitterionic
permeates into brain
dopamine
does not enter brain
enzyme:decarboxylase
catalytic protein Greek, “to leaven”
Another example of neutral drug permeation.
In Parkinson’s Disease: most neurons that make dopamine die (Lecture 25)The challenge: replace the dopamine in the brain
HO
HO
H2C NH3
+
CO2-
HO
HO
H2C
CH2
NH3+
![Page 21: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/21.jpg)
22
Brain Other organs
Protein
Nonpolar molecule
Polar molecule (e. g., glucose)
Endothelial cells form the blood-brain barrier
“Tight junction”
~ 10 m
![Page 22: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/22.jpg)
23
Endothelial cells lining the capillary
Red blood cells
Endothelial cells form the blood-brain barrier
“Tight junction”
Blood vessel
Blood
Glial foot
![Page 23: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/23.jpg)
24
The Structural Basis of
Tight Junctions
Little Alberts, 2nd edFigure 21-22
extracellularspace
![Page 24: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/24.jpg)
25
Acid-base equilibrium and permeability
Uptake from the stomach
Uptake from smoke
Crossing the cell membrane
Short-circuiting synaptic vesicles
Neurotransmitter transport inhibitors
Blood-brain barrier:
molecular basis
an opportunity for drug specificity
a problem for drug delivery
Drugs in the Body and in Cells in Bi 1
Lecture 5
![Page 25: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/25.jpg)
26
nicotine
First uses
Ca. 1550
Both the tobacco plant (Nicotiana tabacum) and the compound are named for
Jean Nicot, a French ambassador to Portugal, who sent tobacco seeds to Paris
in 1550.
![Page 26: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/26.jpg)
27
procaine
Procaine was synthesized originally in 1905 as a replacement for cocaine.
Cocaine became popular in the late 19th Century both as a stimulant and as
an anesthetic. Organic chemists hoped to synthesize compounds that lacked
the stimulant effects but retained the anesthetic effects.
Procaine met these goals. It is still used by dentists.
Similar acting compounds: xylocaine, benzocaine.
First uses
![Page 27: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/27.jpg)
28
morphine
The first recorded reference to the opium poppy, Papaver somniferum was by a Greek writer in the 3rd Century BC.
Morphine was first extracted from the opium poppy in 1806.There are about 20 other alkaloids in opium.
Structure finally solved by Robert Richardson (Nobel Prize 1947)
Derivatives: heroin, codeine, Fentanyl, methadone
Greek, “juice”
“poppy that brings sleep”Genus species
Morpheus, Greek God of dreams
First uses
![Page 28: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/28.jpg)
29
botulinum toxin
First medical use
1970’s
![Page 29: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/29.jpg)
30
botulinum toxin
Botulinum toxin is made by Clostridium botulinum, an anaerobic bacterium.
“Botulism” comes from a German physician who noticed cases of paralysis
associated with eating an uncooked smoked sausage 1793. 13 people in Wildbad
shared the sausage that had been sitting for hours; all became ill and six died. (To
describe their illness, the word botulism was derived from the Latin botulus, for
sausage.)
The conditions beneath the skin of the eaten sausage had been anaerobic (i.e.,
there was very little oxygen in the meat) and enough time had elapsed to allow the
clostridial organisms present to multiply and produce a toxin in the sausage
substance.
Botulinum toxin is fatal in extremely low quantities (10-13 M), because it paralyzes
muscles. 10-8 grams kills a mouse. The paralysis occurs at the synapse.
![Page 30: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/30.jpg)
31
Botulinum toxin is made as a single protein chain, then cleaved
catalytic protein
The light chain enters cells,then acts as an enzyme
![Page 31: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/31.jpg)
32
botulinum toxin
However, many diseases and discomforts are caused by excess muscle activity.
Botulinum toxin, injected in minute quantities, blocks this excess activity and gives
relief from squint and spasm.
Botulinum toxin also decreases frown lines.
![Page 32: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/32.jpg)
33
http://www.botox.com/
![Page 33: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/33.jpg)
34
Dr. Mirabadi Cosmetic Surgeon.URL
http://www.beautifulandhealthy.com/
![Page 34: 1 Bi 1 Lecture 2 Tuesday, March 28, 2006 Revised 4/4/06 What is a drug? nicotinemorphine](https://reader030.vdocument.in/reader030/viewer/2022032605/56649e7f5503460f94b82c91/html5/thumbnails/34.jpg)
35
Warren C. Stout, M.D. - Cosmetic Eye Surgery and Cosmetic Face Surgery.url
http://www.stoutlaser.com/botox.html