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Drugs Drugs and the Brain Brain miniLecture 1A O Organization i ti and dO Overview i module, d l part tA

2012 California Institute of Technology

Whats a Drug?
procaine morphine botulinum toxin



Introducing the Central Nervous System

Top dorsal Front F t rostral Back caudal


Bottom ventral

Spinal cord

The synapse is a point of information processing

presynaptic neuron
Nestler, Hyman, Malenka, Molecular Neuropharmacology, McGraw-Hill Professional Publishing g

postsynaptic neuron
Box 2 - 2 Figure A

An adult human brain contains ~ 1011 neurons, and each of these might receive 103 synapses apiece, apiece for a total of 1014 synapses. Most of these synapses form during the first 2 yr of life. Thus 1014synapses/108 s = 106 synapses/s form in a fetus and infant!

Most drug receptors are membrane proteins (Nicotinic Acetylcholine Receptor)

~ 2200 amino acids in 5 chains (subunits), MW ~ 2.5 x 106

Binding region

Membrane region

Colored by secondary structure

Colored by subunit (chain)

Cytosolic eg o region


Drug receptors are proteins. Heres the acetylcholine binding protein interfacial aromatic box occupied by nicotine

Y198 C2

W149 B

Y93 A

Y190 C1

non-W55 D

(Muscle Nicotinic numbering)

Part 1: Drugs Activate and Block Ion Channels

Ligand-binding region
acetylcholine or nicotine

acetylcholine or nicotine

acetylcholine or nicotine

M1 M2 M3

~ 100 (10 nm)


Part 1: Drugs Activate and Block Ion Channels

Drug Receptor



Part 2: Drugs Act on G protein pathways

Neurotransmitter N t itt or hormone h binds to receptor activates G protein How fast? Ho 100 ms to 10 s How far? Probably less 1 m

Effector: enzyme or channel




Downstream from GPCRs are intracellular messengers. We have several ways to measure them. Live-cell Live cell imaging is one way. Biochemistry is another. Fluorescence Microscopy

Alberts et al., Essential Cell Biology, Garland Science

Drugs Drugs and the Brain Brain See two items on the course Web site: Henry Lesters sources of research funding; and the disclaimer about medical advice End of Organization and overview module, part A
2012 California Institute of Technology