Antagonist / Agonist
Antagonists: Opposes or inhibits effects of a NT on a post-synaptic cell.
Agonists: Facilitates effects of a NT on a postsynaptic cell.
Define Psychopharmacology, drug, drug effects and pharmacokinetics and provide three examples of drugs (one non-medical, please!).
Psychopharmacology: Study of the effects of drugs on nervous system and behavior.
Drug:Exogenous chemical not necessary for normal cellular functioning that significantly alters functions of certain cells at relatively low doses.
Drug effects: Changes we observe in an animal's physiological processes and behavior.
Pharmacokinetics: process that drugs are absorbed / distributed within the body, metabolized, and excreted.
When drugs block reuptake and bind with enzyme so it can no longer destroy NT. This makes the drug an ______.
When a drug selectively activates a presynaptic autoreceptor and decreases NT release, it acts as an _______.
When the drug blocks presynaptic autoreceptors and increases the release of NT, it acts as an _______.
1. Agonist.
2. Antagonist.
3. Agonist.
1. Explain EPSP and IPSP-hyper-polarized / de-polarized, and what it means in terms of the resting potential.
2. What are amino acids and what do some amino acids also act as?
Share whether Glycine, GABA, Glutamate are excitatory or inhibitory and explain where Glycine, GABA, Glutamate are found.
1. ESPS - depolarization - less negative than resting - 70) ie: more positive.
ISPS - hyperpolarization - becomes more negative.
2. Amino acids are building blocks of proteins. Some act as neurotransmitters.
Glutamate: excitatory - brain. GABA: inhibitory - brain. Glycine: inhibitory - in spinal cord and lower brain stem.
These drugs affect the release of _____________.
•Botulinum toxin
•Black widow spider venom
•Neostigmine & Physostigmine
Affect receptors:
•Atropine (e.g., belladonna)
•Curare
Acetylcholine
Drug blocks autoreceptors; increases synthesis / release of NT
AGO
Name five overall methods for drug administration and how they are absorbed into the body.
METHODS:
Intravaneous (IV) injection - injected directly into vein.
Intramuscular (IM) injection - injected directly into muscle and absorbed through capillaries.
Subcutaneous (SC) injection - injected directly into the space beneath the skin.
Intraperitoneal injection - mostly used on small animals and put into peritoneal cavity.
Oral administration - via the mouth
Inhalation - inhaled into the lung (only works for vapors)
Topical administration - directly onto skin or mucous membrane
Nasal insufflation - sniffing to contact nasal mucosa
Intracerebral administration - directly into the brain
Intracerebroventricular (ICV) administration - directly into one of the cerebral ventricles
In effects of production of neurotransmitters:
_____ help NT synthesis.
Drugs can inactivate _____ that control synthesis and act as a antagonist.
Enzymes.
What are the main Glutamate receptors and which one is important for learning and memory?
Ionotropic: NMDA, AMPA, kainate
Metabotropic glutamate receptor
NMDA: needs both voltage and ligand to open - glutamate opens channel; depolarization removes Mg2+) -> coincidence detector. Blocking the glutamate binding site on NMDA receptor impairs learning and memory.
What is a monoamine? Name the five types of monoamines and if they are catecholamines or indolamines. Name which amino acid they are derived or synthesized from.
Destruction of _________ (catecholamines / indolamines) regulated by enzyme MAO (monamine oxidase) located in presynaptic terminal.
Monoamines: synthesized by a single amino acid.
Dopamine : Catecholamines - synthesized from tyrosine
Norepinephrine : Catecholamines - synthesized from tyrosine
Epinephrine : Catecholamines - synthesized from tyrosine
Serotonin : Indolamine - synthesized from tryptophan
Histamine : Indolamine -derived from histidine
-catecholamines
Drug inactivates synthetic enzyme ; inhibits synthesis of NT
ANT
Explain the relationship between lipid solubility and drug site distribution, as well as which types of administration are faster than others / slower than others. Explain why.
Drugs most often act in CNS. Different drugs reach blood plasma faster. Lipid solubility has to do with the speed at which molecules can pass through the cells that line the capillaries in the blood brain barrier (within CNS). Drugs that are lipid soluble will be faster at this and provide faster results of said drug.
Intravaneous is the fastest, then smoked, then intranasal, then then oral. Oral is the slowest because it has to go through stomach, most filtered through liver / kidneys, etc. Intravaneous direct to vein which goes to the brain -> BBB fastest.
______ necessary to allow NT to be synthesized.
Drugs can be a _____ and act as agonist.
(L-DOPA -> Dopamine).
Precursors.
What bind to second site on GABA receptors and what are they (antagonists / agonists / direct / indirect)?
Benzodiazapines:
•diazepam (Valium)
•reduce anxiety -anxiolytic
•promote sleep
•reduce seizure activity
•produce muscle relaxation
•indirect agonist
Which monoamine is this describing:
Implicated in movement, attention, learning, reinforcement
Implicated in Parkinsons
3 most important systems of _________ neurons:
Nigrostriatal: from substantia nigra to basal ganglia
Mesolimbic: from ventral tegmental area to limbic regions
Mesocortical: from VTA to prefrontal cortex
Dopamine
Drug inactivates acetylcholinesterase
AGO
Explain the relationship between the Dose-Response Curve, the Therapeutic Index, and the Margin of Safety.
What is the ideal: eg: effectiveness and potency in regards to therapeutic index?
Dose response curve: Graph of magnitude of a drug effect as a function of the drug administered.
Therapeutic index: Ratio between dose that produces desired effect in 50% of tested animals and dose that produces toxic effects in 50% of animals. The measure between that is the margin of safety.
Storage and Release:
1. Antagonists _____ (block / open) vesicle transporter molecules.
2. Affect NT release at _____________ (location).
Option 1: _______ (activate / deactivate) and _______ (open / prevent) vesicle from ______ (releasing / fusing) with membrane, making it an antagonist.
Option 2: Bind with ______ (proteins / enzymes) and trigger NT release, making it an agonist.
1. Block.
2. Terminal Button.
Option 1: Deactivate, prevent, fuse
Option 2: Proteins
Glycine is an _______ transmitter that controls the spinal cord and lower portions of the brain.
It is an ______ (ion/mono-tropic) and controls a ___ (Cl- / Ca+) channel.
BONUS POINT:
What bacteria is linked to this amino acid?
Inhibitory
Ionotropic
Cl-
Bonus: Tetanus
Describe peptides. What are they? Where are they synthesized? What is released with them to regulate receptor sensitivity to the neurotransmitter? Where are they released?Who destroys them? What do we call a family of peptides and what do they act as? What does the family of peptides do?
Peptides: 2 or more amino acids linked by peptide bond. CNS releases lots of different ones and they're synthesized in the soma. Released with neurotransmitters from all parts of terminal button. Destroyed by enzymes. Act has endogenous opioids (endorphins!) and provide analgesia, inhibits species-typical defensive response, and reinforcement.
Drug blocks postsynaptic receptors
ANT
Explain affinity, efficacy, tolerance, withdrawal and sensitization, and placebos.
Provide examples of each.
Also include brief explanations of compensatory mechanisms.
Affinity: The readiness with which two molecules join (morphine has a higher affinity than aspirin)
Efficacy: Relationship between receptor occupancy and ability to initiate a response. (Aspirin should remove a headache but it is not meant to treat a dismembered arm.)
Tolerance: Decrease in effectiveness of a drug that is administered repeatedly. More drug needed to reach same effect. (Needing higher doses of caffeine to feel "awake").
Withdrawal: Symptoms opposite to those produced by drug when it is administered repeatedly and then suddenly removed. (Brain zaps after SSRI removed).
Sensitization: Reverse tolerance - when repeated exposure of the same dose of a particular drug of abuse creates a stronger response. Happens most with psycho-stimulants (MDMA / cocaine).
Placebos: Inert substance given in lieu of physiologically active drug. (Sugar pill).
Compensatory mechanisms:
-Decrease in binding effectiveness at receptor level: where receptors become less sensitive (decrease affinity) or decrease in receptor number.
-Process of coupling receptors to ion channels where: process becomes less efficient, decreased efficacy, promotes tolerance.
Explain competitive binding (drug binds with receptors at same site as NT) for direct agonists and direct antagonists.
Explain noncompetitive binding (does not interfere with binding site for principal ligand (NT)) for indirect agonists and indirect antagonists.
COMPETITIVE BINDING:
Direct agonist
-Binds with & activates receptor
-Acts like the NT
Direct antagonist (receptor blocker)
-Binds with receptor, but does not activate it
-prevents natural ligand (NT) from binding with receptor
NONCOMPETITIVE BINDING:
-Indirect agonist: attaches to alternative binding site on receptors (not binding site of principal ligand) and facilitates action of receptor.
-Attaches to alternative binding site on receptor (not binding site of principal ligand) and interferes with action of receptor.
Modulating Neurotransmitters's roles: Share main purpose of each.
Acetycholine
Norepinephrine
Serotonin
Dopamine
Acetylcholine: learning, muscles
Norepinephrine: increases vigilance
Serotonin: stabilizes mood, reduces impulsivity
Dopamine: activates voluntary movement in some areas, reinforces on-going behavior in others, reward pathways.
Which one is described here: Soluble gases / Lipid / THC / Nucleosides:
Compound consisting of a sugar molecule with a purine or pyrimidine base, with Adenosine as one of the compounds.
•Neuromodulator in brain with an inhibitory effect on behavior. It is released when cells are short of fuel or oxygen and helps nearby blood vessels to dilate, increasing blood supply to area. Accumulates while awake, decreases during sleep. Blocked by caffeine- which produces excitatory effects.
Nucleosides.
THC: Analgesic / stimulates appetite, suppresses nausea, relieves asthma attacks, etc. Interferes with concentration and memory, alters visual and auditory perceptions.
Lipids: Substances derived from lipids transmit messages within or between cells. Synthesized and released on demand - not stored in vesicles. Best known are endocannabinoids - natural ligands for receptors responsible for physiological effects of THC.
Soluble gases: neurons use at least 2 gases to communicate - nitric oxide (increase blood flow to brain area being used and dilates blood vessels) and carbon monoxide (involved in control of intestinal wall muscles; dilates blood vessels in brain).