Agonists and antagonists

Ligand

Any substance that can bind to a receptor

Endogenous

NT, hormones

Exogenous

External substances that can also bind to receptors and sometimes cause an effect

exogenous medicines

prescription drugs, over the counter drugs

exogenous recreational substances

drugs of abuse, recreational drugs (could be therapeutic)
toxins

Neuropharmacology

study of effects of drugs on the nervous system

agonist

bind to a receptor and activate it
mimic or potentiate the actions of a NT

partial agonist

bind and activate the receptor, but produce a weaker response than a full agonist

inverse agonist

bind to a receptor and reduce its activity below its baseline, producing the opposite effect of the NT
decrease in signaling

antagonists

bind to a receptor but doesn’t activate it, just prevents binding by other ligands.
also called receptor blockers

competitive ligands

bind to the same part of the receptor molecule as the NT
competes with the NT for binding
may activate or block the receptor

what does adding more NT do

can outcompete the ligand

noncompetitive ligands

bind to alternative modulatory sites
may activate or prevent the receptor from being activated (noncompetitive agonist or noncompetitive antagonist)

what does adding more NT do for noncompetitive ligands

effect cannot be overcome

Effect of activating all receptors of a NT

can have several unintended side effects

How do drug molecules spread throughout the body

briefly binding to their receptors upon encounter

drug development

can be developed to bind to just one or a few receptor subtypes

binding affinity

how strongly the ligand binds to the receptor

high affinity

binds tightly and stays bound longer. Receptor is activated or blocked more effectively at lower concentrations

low affinity

binds weakly, requires higher concentrations to have an effect
NT are low affinity ligands, can rapidly dissociate from receptors

efficacy

ability of a bound ligand to activate the receptor

agonist efficacy

high efficacy

antagonist efficacy

low efficacy

partial agonist effiacy

produce a medium response regardless of dose

dose response relationship

combination of affinity and efficacy determines overall action of a drug

potency

dose of the drug need to produce an effect

how do greater doses produce greater effects

larger dose of the drug increases proportion of receptors bound by the drug

Dose response curve (DRC)

graph of the relationship between drug doses and effect
DRCS show the effective dose range of a drug

what is DRC used for

to understand pharmaco-dynamics: the functional relationship between drugs and their targets

Bioavailability

portion of a drug that is free to act on its target

affected by route of administration

determines how much of the drug reaches the brain and how quickly

fast acting routes

smoking (inhalation), intravenous injection

slow acting routes

oral ingestion (gradual buildup of drug concentration over time)

Blood brain barrier

tight junctions within the CNS prevent the movement of large molecules and can limit drug availability
many drugs that might be useful are too large to pass the BBB to enter the brain

Ingestion

tablets, capsules, syrups, infusion or tea, suppository

ingestion speed

depends on absorption by the gut, affected by digestive processes and the presence of food
slow to moderate speed

inhalation

nasal absorption, inhaled powder, gases and sprays, smoking

inhalation route and speed

rich vasularization of the nose and lungs sends it directly into the bloodstream
moderate to fast speed

peripheral

subcutaneous, intramuscular, intraperitoneal (abdominal), intravenous (IV)

peripheral speed

differences in speed reaching the bloodstream (IV faster)
moderate to fast speed

central injection

intracerebroventricular (into ventricular system), intrathecal (into spinal CSF) epidural (under the dura meter), intracerebral (into brain region)

central injection speed

circumvents the blood brain barrier, more commonly used in research
fast to very fast speed

pharmacokinetics

study factors that affect movement of a drug through the body
Describes stages of absorption, distribution, metabolism, and excretion of drugs

biotransformation

produces active metabolites that may produce side effects

tolerance

successive exposures have decreasing effects
larger doses of the drug are needed to get the same effect
withdrawal symptoms may be caused by drug tolerance

metabolic tolerance

organ systems become more effective excreting the drug
eg liver becomes more effective at eliminating the drug

functional tolerance

target tissue may show altered sensitivity to the drug, changes in the number of receptors

cross tolerance

tolerance to a whole class of chemically similar drugs