NEUR 2600 Lecture Notes - Lecture 6: Mescaline, Procaine, Cerebral Circulation
CHAPTER 6: HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND
BEHAVIOUR
Principles of psychopharmacology
● Study of the ways drugs affect the nervous system and behaviour
● Drugs
○ Chemical compounds administered to produce a desired change
● Psychoactive drug
○ Substance that acts to alter mood, thought, or behaviour, used to manage
neuropsychological illness
● Drug routes into the nervous system
○ Routes of drug administration
■ To be effective, a psychoactive drug has to reach its nervous system
target
■ Drugs can be administered orally, inhaled, administered through rectal
suppository, absorbed from a patch applied to the skin or mucous
membranes, or injected into the bloodstream, into a muscle, or even into
the brain
○
○ Oral administration is easy and convenient but has the most barriers to the brain
○ There are fewer barriers for a drug destined for the brain if the drug is injected
directly into the bloodstream
○ Fewest barriers are encountered if a psychoactive drug is injected directly into
the brain
○ With each barrier eliminated en route to the brain, the dose of a drug can be
reduced by another 90%
● Revisiting the blood-brain barrier (BBB)
○ The body presents a number of barriers to the internal movement of drugs: cell
membranes, capillary walls, the placenta
○ BBB prevents most substances, including drugs, from entering the brain via the
bloodstream
○ Endothelial cells in capillaries throughout the body are not tightly joined; it’s easy
for substances to move into and out of the bloodstream
○ Endothelial cell walls in the brain are fused to form tight junctions, so most
substances cannot squeeze between them
○ Endothelial cells of brain capillaries are surrounded by the end feet of astrocytes
attached to the capillary wall, covering about 80% of it
○ Glial cells provide a route for the exchange of food and waste between capillaries
and the brain’s extracellular fluid; and from there to other cells
○
○ Blood-brain barrier-free regions
■ The area postrema allows toxic substances in the blood to trigger a
vomiting response
■ The pineal gland enables hormones to reach it and modulate the
day-night cycles controlled by this structure
● Gaining access to the brain
○ Small, uncharged molecules (e.g. oxygen and carbon dioxide) are fat soluble and
can freely cross the BBB
○ Larger charged molecules (e.g. glucose, amino acids, fats) must be actively
transported across the BBB
○ Difficulty developing drugs for the brain
■ Estimated 98% of drugs that may affect brain function and have
therapeutic use cannot cross the BBB
● How the body eliminates drugs
○ Drugs are broken down (catabolized) in the kidneys, liver, and intestines
○ Drugs are excreted in urine, feces, sweat, milk, and exhaled air
○ Some substances that cannot be removed may build up in the body and become
toxic
○ The liver is especially active in catabolizing drugs
○ The cytochrome P450 enzyme family are involved in drug catabolism
○ The liver is capable of catabolizing many drugs into forms that are more easily
excreted from the body
● Drug action at synapses
○ Most psychoactive drugs exert their effects by influencing synaptic chemical
signaling
○ Agonist
■ Substance that enhances the function of a synapse
○ Antagonist
■ Substance that blocks or decreases the function of a synapse
○ Synthesis of neurotransmitter in cell body, axon, or terminal
○ Storage of neurotransmitter in granules or vesicles
○ Release of neurotransmitter from presynaptic terminal
○ Receptor interaction in postsynaptic membrane
○ Inactivation of excess neurotransmitter at the synapse
○ Reuptake into the presynaptic terminal
○ Degradation of excess neurotransmitter
○ A drug can modify seven major chemical processes
■
○ Example of drug action: acetylcholine synapse
■ Agonists excite muscles, increasing muscle tone
■ Antagonists inhibit muscles, decreasing muscle tone
■ Drugs affect synthesis, release, binding to the postsynaptic receptor,
breakdown or inactivation
Document Summary
Chapter 6: how do drugs and hormones influence the brain and. Study of the ways drugs affect the nervous system and behaviour. Chemical compounds administered to produce a desired change. Substance that acts to alter mood, thought, or behaviour, used to manage neuropsychological illness. To be effective, a psychoactive drug has to reach its nervous system target. Drugs can be administered orally, inhaled, administered through rectal suppository, absorbed from a patch applied to the skin or mucous membranes, or injected into the bloodstream, into a muscle, or even into the brain. Oral administration is easy and convenient but has the most barriers to the brain. There are fewer barriers for a drug destined for the brain if the drug is injected directly into the bloodstream. Fewest barriers are encountered if a psychoactive drug is injected directly into the brain. With each barrier eliminated en route to the brain, the dose of a drug can be reduced by another 90%
