Drugs
Fall 2002

Most drugs (illegal, legal, prescription, etc.) change behavior by altering the actions of neurotransmitters. For example, drugs can alter:

Synthesis--inhibit enzymes (alpha-methyltyrosine inhibits tyrosine hydroxylase)
Storage--disrupt vesicles (reserpine)
Release--stimulate release (amphetamine)
Removal--
        Block reuptake (Prozac or fluoxetine)
        Block enzymatic degradation--(Pargyline, an MAO inhibitor) Two terms commonly used to describe the action of drugs are:
Agonists mimic the effects of a neurotransmitter
Antagonists block the effects of a transmitter

For example,

Heroin is an agonist that mimics the effects of naturally occurring opioids such as enkephalin
Naloxone is an antagonist that binds to opioid receptor preventing opioids from binding.
 
Receptors located on the presnyaptic terminal, called  autoreceptors,  regulate the release of neurotransmitter. Drugs can come from many different sources. Some examples include:
Drug
Source
NS mechanism
Behavioral effect
Tetrodotoxin
Puffer fish
Plugs Na+ channels
Death
Ethanol
Yeast metabolism
Facilitates GABA
Loss of judgement & coordination
Botulinus toxin
Bacteria
Inhibits ACh release
Paralysis
Physostigmine
Calabar bean
Inhibits breakdown of ACh
Convulsions
Cocaine
Coca leaves
Inhitits DA reuptake
Euphoria and hyperactivity

Drugs are delivered to the nervous system by blood vessels. There are many different ways to get drugs into the vascular system.
 

 The differences in the chemical structure between drugs affects how the drug is distributed in the body. Specifically,

1. Absorption--How easily does the drug get into the blood?
2. Distribution--How easilty does the drug cross membranes to get from the blood to the target (e.g., the blood brain barrier)?
3. Elimination--How long does the drug last once it is in the body?
The point at which half of the drug has been  inactivated is called the drugs half life.
These factors are called drug pharmacokinetics (the body's action on the drug or the movement of drugs in the body)
An example of opioid pharmacokinetics is shown in the table below. Oral availability is the amount of drug that gets into the blood following oral administration.
 
Drug
Oral Availability
Half Life
morphine
24%
1.9 hours
heroin
0%
3 min
methadone
92%
35 hours

Once in the body, drugs go everywhere the blood goes. The body tries to remove drugs from the system by inactivating them (especially in the liver) and excreting them (kidneys). However, some drugs are stored in fat and and remain in your system for months.
 

Chronic drug use causes the nervous system to adapt. These are known as pharmacodynamic changes (drug action on the body).
 

Some of the terms associated with drug abuse are:

Addiction--compulsive use of a drug. Addiction appears to involve a brain structure called the nucleus accumbens.
Tolerance--progressive decrease in response to a drug. This can occur in one of two ways:
Pharmacokinetic--a change in drug metabolism and/or distribution
Pharmacodynamic--a change in neural response to the drug
Dependence--a situation where a drug is required to function normally. Removal of the drug induces withdrawal symptoms


Some common drugs and their mechanism of action include:
 
Drug Transmitter System Mechanism
Nicotine Acetylcholine receptor agonist
Ecstasy Serotonin blocks reuptake (also facilitates DA)
Ritalin Dopamine Stimulates DA release
Cocaine Catecholamines blocks reuptake
Valium GABA enhances opening of Cl- channels

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