Lecture 6 Flashcards
Chapter 4
define Drug
An exogenous chemical that at relatively low doses significantly alters the function of certain cells
define Psychopharmacology
Study of effects of drugs on the nervous system and behavior
define Drug effect
The changes a drug produces on physiological processes and behavior
define Site of action
Location at which molecules of a drug interact with molecules located on or in cells of body, affecting some biochemical processes of these cels
how to CATEGORIZING DRUGS
Many drugs directly or indirectly alter the activity of receptor proteins.
A receptor agonist is what
a drug that (through any means) increases the activity of the receptor protein.
A receptor antagonist is what
a drug that (through any means) decreases the activity of the receptor protein
A partial agonist is what
a drug that partially activates a given receptor (relative to a fullagonist)
A partial antagonist is what
a drug that partially decreases the activity of the receptor protein (relative to a full antagonist).
These classes of drugs can bind one of 2 ways:
competitively or non-competitively
wha are the different categorizing of drugs
A receptor agonist
A receptor antagonist
A partial agonist
A partial antagonist
what does A direct agonist d
acts similarly to the endogenous neurotransmitter. It activates the receptor by attaching itself to the binding site where the neurotransmitter would normally bind.
what does A direct antagonist do
attaches to the binding site but it prevents the receptor from being activated.
The competition for a receptor binding site between an endogenous neurotransmitter and an exogenous drug will depend on what
their relative concentrations and their affinity for the binding site
The competition for a receptor binding site between an endogenous neurotransmitter and an exogenous drug will depend on their relative concentrations and their affinity for the binding site. The likelihood or strength of ligand-receptor binding is called what
affinity
If a receptor is highly active to begin (e.g., due to endogenous neurotransmitter signaling), then a competitive partial agonist with very high affinity for the binding site can produce what
the same effect as a partial antagonist
what is non-competitive binding
When a drug binds to a receptor at a site that does not interfere with the binding site of the principal ligand it is called non-competitive binding
is it possible for a neurotransmitter to bind on one site of a receptor while a drug binds on another in non-competitive binding
It is
how does An indirect agonist do noncompetitive binding
does so in a manner that facilitates activation of the receptor
how does An indirect antagonist do noncompetitive binding
does so in a manner that prevents activation of the receptor
A non-competitive antagonist doesn’t compete with an endogenous signaling molecule for a particular binding site. It wins how
by binding to an alternative site.
define Allosteric Modulator
Drug that binds non-competitively and influences (modulates) the effect of a primaryligand. Positive allosteric modulators amplify the effect of the primary ligand. Negative allosteric modulators reduce the effect of the primary ligand.
what are The Conventional Neurotransmitters
Glutamate
GABA
Dopamine
Norepinephrine
Acetylcholine
Serotonin
what is Glutamate
Main excitatory neurotransmitter in the brain
wha is GABA
Main inhibitory neurotransmitter in the brain
what are Dopamine Norepinephrine Acetylcholine Serotonin considered
Main neuromodulators in the brain
what is different about neuromodulators
Although these neuromodulators are indeed conventional (classic) neurotransmitters like glutamate and GABA, most of their receptors are metabotropic (as opposed ionotropic) and they tend to produce a more modulatory influence on postsynaptic cell activity (instead of causing a fast EPSP or IPSP).
More than 99% of neurons release one of these two neurotransmitters:
Glutamate
GABA
is Glutamate excitatory or inhibitory
Typically excitatory (the gas pedal)
is GABA excitatory or inhibitory
Typically inhibitory (the brakes)
Ionotropic glutamate receptors induce what
Ionotropic glutamate receptors induce excitatory post-synaptic currents (EPSCs) and membrane depolarization, perhaps an action potential
Ionotropic GABA receptors induce what
Ionotropic GABA receptors induce inhibitory post-synaptic currents (IPSCs) and membrane hyperpolarization
Glutamate agonists do what
Agonists: often cause seizures and excitotoxicity (kainic acid, NMDA)
GABA agonists do what
Antagonists: often cause seizures
Glutamate Antagonists do what
Antagonists: dissociative anesthetics (ketamine, PCP)
GABA Antagonists do what
Agonists: anesthetics, anticonvulsants, muscle relaxants, sleeping pills, anti-anxiety (alcohol, barbiturates, benzodiazepines)
In addition to glutamate or GABA, many neurons also co-release what
neuromodulators and/or neuropeptides.
The Neuromodulators are made of what
These neurotransmitters are made in a small collection of neurons that send their axons out widely
Neuromodulators are distinguished as neuromodulators because
they don’t typically produce simple excitatory or inhibitory effects in the CNS
most of their receptors are G-protein coupled receptors, not ion channels
they often diffuse short distances outside of the synapse and can influence activity of neighboring neurons
Serotonin, dopamine, and norepinephrine all have a similar chemical structure and are known as what
monoamines
Within the monoamine category of neurotransmitters, there are what
catecholamines (dopamine and norepinephrine) and indolamines (serotonin).
what re the 3 categories of Neurotransmitters
Conventional neurotransmitters
Neuropeptides
Lipid-based signaling molecules
give characteristics of Conventional neurotransmitters
mostly amino acid derivatives
The main players: glutamate, GABA, dopamine, serotonin, norepinephrine, acetylcholine
are synthesized locally in axon terminals
are usually secreted from small synaptic vesicles that dock very close to the site of Ca2+entry in the axon terminal
generally activate ionotropic and metabotropic receptors
are typically recaptured after secretion and reused
usually bind receptors directly across the synapse. Even when neurotransmitters diffuse, they only act over distances of tens to hundreds of micrometers.
give characteristics of Neuropeptides
short string of amino acids (i.e., a protein formed with only ~ 10-30 amino acids)
Examples from the list of >70: oxytocin, vasopressin, enkephalin, prolactin, NPY, ghrelin, CRH
are synthesized in the cell soma, transported down the axon while undergoing additional processing, and released just once.
are usually secreted from large dense core vesicles that dock a ways back from the site of Ca2+entry in the axon terminal
only activate metabotropic receptors (neuropeptides do not activate ionotropic receptors)
no synaptic recylcing occurs of either the neuropeptides or their immediate precursors.
may diffuse long distances and exert action at a distance (non-synaptic communication)
give characteristics of Lipid-based signaling molecules
(e.g., the cannabinoids anandamide and arachidonoylglycerol)
are synthesized and released on demand (as needed; the details remain murky)
are secreted in an unknown, non-vesicular manner typically from postsynaptic neurons
activate metabotropic receptors typically located on the presynaptic axon terminal
who is the Godfather of Molly
Sasha Shulgin
What are the similarities of Heroin, morphine and Imodium Anti-Diarreal
They are all very strong opiates
What are the differences of Heroin, morphine and Imodium Anti-Diarreal
heroin– crosses the blood-brain barrier quickly because it is very lipid (fat) soluble.
morphine– crosses the blood-brain barrier a bit slower because it is less lipid soluble.
imodium– does not cross the blood-brain barrier.
define Pharmacokinetics
Process by which drugs are absorbed, distributed within the body, metabolized, and excreted
Drugs have to reach their site of action which is what
the point where drug molecules interact with molecules located on or in cells of the body.
what is Intravenous (i.v.) injection
into the vein
what is Intraperitoneal (i.p.) injection -
into the abdominal wall (peritoneal cavity)
what is Intramuscular (i.m.) injection -
into the muscle
what is Subcutaneous (s.c.) injection -
into the space between the skin
what is Oral administration
- by mouth
what is Sublingual administration -
under the tongue
what is Intrarectal administration –
in the rectum as a suppository
what is Inhalation -
by smoking
what is Topical administration –
on the skin
what is Intracerebral administration -
directly into the brain
what is Intracerebroventricular (ICV) –
into a cerebral ventricle
what is Intrathecal (epidural) –
into the cerebrospinal fluid of the spinal cord
The speed of drug absorption into the blood and the extent to which the drug might be metabolized before getting to the blood or to the brain are heavily influenced by what
the route of administration
what are Principles of PsychopharmacologyInactivation and Excretion
Drugs do not remain in body indefinitely
Many drugs are deactivated by enzymes in the liver and blood, and all are eventually excreted, primarily by kidneys
The brain also contains enzymes that destroy some drugs
what is A dose response curve
is a graph of the magnitude of an effect of a drug as a function of the amount that is administered. It is obtained by giving subjects various doses of drug (typically according to weight).
Higher doses cause larger effects until when
the point of maximum effect
what is the margin of safety
The difference between the two curves is the drugs margin of safety – often conveyed as therapeutic index: the ratio between the dose that produces desired effect in 50 percent of animals and the dose that produces toxic effects in 50 percent of animals
Drugs that fully activate (or inactivate) the same receptor can vary in effectiveness because:
They have different sites of action (competitive vs non-competitive).
They have different pharmacokinetics (heroin vs morphine).
They have different affinities for the molecules to which they attach. The affinity of a drug is the readiness with which two molecules join together.
a) A drug with a high affinity will produce an effect at low doses whereas a drug with a low affinity may have to be administered at a high dose.
b) A single drug can have a high affinity at one site of action and a low affinity at a different site of action.
what is Tolerance
when the effect of drug diminishes because of repeated administration. It is the body’s attempt to compensate for the effects of the drug.
E.g., a regular heroin user must take larger and larger amounts of the drug to keep feeling the same effect. Having developed tolerance to heroin, the user will suffer withdrawal symptoms which are opposite effects of the drug (i.e. euphoria vs dysphoria).
E.g., barbiturates have sedative and depressive effects. The sedative effect shows tolerance but the depressive effect does not. Thus, if larger doses of barbiturates are taken to achieve a sedative effect, you run the risk of taking a dangerously high dose of the drug.
what is Sensitization
occurs when a drug becomes more and more effective through repeated use.
what is placebo
A placebo is an inert substance that has no direct physiological effect. It is given to subjects to control the effects of mere administration of a drug
what are the Effects of Repeated Administration
Tolerance
Sensitization
placebo
what re the Effects on Production of Neurotransmitters (from drugs)
Neurotransmitters are synthesized from precursor molecules
Steps in synthesis of neurotransmitters are controlled by enzymes
The packaging of neurotransmitter into synaptic vesicles can be blocked by a drug
Some drugs act as antagonists by preventing release of synaptic vesicles from the axon terminal
Other drugs have just the opposite effect:
They act as agonists by binding with vesicle
The clearance of neurotransmitters is controlled by proteins
define Neurotransmitters are synthesized from precursor molecules
In some cases the rate of synthesis and release of a neurotransmitter is increased when a precursor is administered
In these cases, the precursor itself serves as an agonist
explain Steps in synthesis of neurotransmitters are controlled by enzymes
Therefore, if a drug inactivates one of these enzymes, it will prevent the neurotransmitter from being produced.
Such a drug serves as an antagonist
explain The packaging of neurotransmitter into synaptic vesicles can be blocked by a drug
These drugs act as antagonists because the synaptic vesicles remain empty and nothing is released when they eventually fuse with the presynaptic membrane
explain Some drugs act as antagonists by preventing release of synaptic vesicles from the axon terminal
They do so by deactivating proteins that cause synaptic vesicles to fuse with presynaptic membrane and expel their contents into synaptic cleft
explain Other drugs have just the opposite effect:
They act as agonists by binding with vesicle release machinery or reuptake transporters and directly trigger the release of neurotransmitter
explain The clearance of neurotransmitters is controlled by proteins
Drugs that affect neurotransmitter clearance can act as agonists or antagonists.
The clearance of neurotransmitters is achieved by reuptake into the axon terminal, enzymatic destruction, or diffusion.
what is Acetylcholine
In the central nervous system acetylcholine is often classified as a neuromodulator. (It is made in a small collection of neurons that send their axons out widely. It typically acts to regulate the efficacy of glutamatergic and GABAergic synapses.)
However, acetylcholine is also the primary neurotransmitter secreted by efferent axons that leave the central nervous system. All muscular movement is accomplished by the release of acetylcholine.
All motor neurons release what as their main neurotransmitter
acetylcholine
Most sensory neurons release what as their main neurotransmitter.
glutamate
what does Black widow spider venom
do
Poison produced by the black widow spider that triggers the release of acetylcholine
what does Botulinum toxin (botox
do
Produced by a baterium that can grow in improperly canned food. It is a acetylcholine system antagonist, because it prevents the release acetylcholine causing muscle paralysis
The synaptic vesicle recycling machinery (i.e., endocytosis-driven synaptic vesicle reformation) is another target for what
drugs and toxins
what is Neostigmine
Drug that inhibits activity of acetylcholinesterase, which is the enzyme that breaks down acetylcholine in the synaptic cleft. Neostigmine causes acetylcholine to hang around in the synapses for a longer period of time.
what is Myasthenia Gravis
hereditary disorder in which the person’s own immune system attacks healthy acetylcholine receptors.
People with this disorder become noticeably weaker and weaker over time (fatigability).
We don’t yet have a good way to give these people back functional receptors, but with drugs like Neostigmine we can make the released acetylcholine stay around for longer periods of time
what is Parkinson’s disease
a neurological disorder that is often characterized by tremors, rigidity of limbs, poor balance, and difficulty initiating movements.
It is caused by the degeneration (death) of dopamine neurons in the midbrain.
L-Dopa is often used to treat Parkinson’s disease because it increases dopamine production in the brain and thus acts as a dopamine agonist.
what do Methylphenidate,
Cocaine
do
Drugs that inhibit the reuptake of catecholamine neurotransmitters (dopamine & norepinephrine) by blocking their synaptic transporters.
Tylenol (acetaminophen) does the same thing to one of the cannabinoid reuptake transporters. Elevating synaptic endocannabinoids levels may result in pain relief
what do Adderall,
Crystal meth
do
Drugs that reverse catecholamine transporters, causing dopamine and norepinephrine molecules to flow directly out of the presynaptic terminal (non-vesicular release).
Ecstasy (MDMA) does a similar thing to all of the monoamine transporters (i.e. causes them to run backwards).
what is an example of Receptor blockers
Antipsychotics
(neuroleptics
what do Antipsychotics
(neuroleptics
do
Class of drugs used to treat psychosis (schizophrenia). They are typically dirty drugs (i.e. they have many sites of actions), but most prominently they block one of the dopamine receptors, the D2 receptor.
define allosteric modulator
Drug that binds non-competitively and influences (modulates) the effect of a primaryligand. Positive allosteric modulators amplify the effect of the primary ligand. Negative allosteric modulators reduce the effect of the primary ligand.
