Neuropharmacology, Drugs, Reward Circuitry Flashcards
Neurochemistry
focuses on the basic chemical composition and processes of the nervous system
Neuropharmacology
the study of compounds that selectively affect the nervous system
Receptor Subtypes
defined by the pharmacological characteristics of the site and is based on the availability of selective agonists and antagonists for the subtypes
Types of Neurotransmitters:
Amine, Amino Acid, Peptide, and Gas
Amine
—acetylcholine, dopamine,
serotonin
Amino Acid
—GABA, glutamate
Peptide
—short chain amino acids
(neuropeptides)
Gas
—soluble gases; nitric oxide, carbon
dioxide
Co-Localization (Co-Release)
some neurons contain more than one type of neurotransmitter.
The Main Excitatory Neurotransmitters are
Glutamate and Aspartate
Acetylcholine (ACh)
First neurotransmitter to be identified
Cholinergic
Neurons that use ACh
Two types of ACh Receptors
Nicotinic and Muscarinic
Nicotinic(nAch)
most are inotropic and excitatory, fast and in muscle junctions
Muscarinic
G protein-coupled (metabotropic), slower; excitatory or inhibitory
Nucleus Cholinergic Cell Bodies
Basal Forebrain: Nucleus Basalis and the Medial Septal Nucleus
Monoamine Neurotransmitters
Catecholamines and Indoleamines
Catecholamines
dopamine, epinephrine, and norepinephrine
Indoleamines
melatonin and serotonin
Where is Dopamine(DA) found in neurons:
Mesostriatral Pathway and Mesolimbocortical DA Pathway
Mesostriatal Pathway
important in motor control; neuronal loss is a cause of Parkinson’s disease
Mesolimbocortical DA pathway
involved in reward, reinforcement, and learning; abnormalities are associated with schizophrenia.
Serotonin, 5-HT (5-hydroxytryptamine)
- most cell bodies are in raphe nuclei; their serotonergic fibers project widely.
- Serotonin is implicated in sleep states, mood, sexual behavior, and anxiety.
- Antidepressants, such as Prozac, increase
5-HT activity—effects depend on which
receptor subtypes are affected.
Norepinephrine, NE (noradrenaline)
- Released from the locus coeruleus in
the pons and lateral tegmental system in
the midbrain - Cells producing it are noradrenergic.
- NE systems modulate processes
including mood, arousal, and sexual
behavior.
Opioid Peptides
mimic opiate drugs such as morphine (enkephalins and endorphins)
Nitric Oxide (NO)
is a gas neurotransmitter that is produced in locations other than axons and not held in vesicles. It does not interact with membrane-bound
receptors; diffuses out of and into cells. And it can act as a retrograde transmitter
Ligand
a substance that binds to a receptor
Agonist
initiates normal effects of the transmitter on that receptor
Antagonist
binds to a receptor and does not activate it, prevents binding by other ligands
Inverse Agonist
initiates the reverse of the normal affect
Competitive Ligands
they bind to the same part of receptor molecule as
an endogenous ligand. Can be agonists, antagonists, or inverse agonists
Noncompetitive Ligands
bind to modulatory sites that are not part of the
receptor complex
Binding Affinity
degree of chemical attraction between ligand and receptor
- A drug with a high affinity for its receptor
will be effective at very low doses.
- Neurotransmitters are low-affinity ligands;
can rapidly dissociate from receptors.
Efficacy
ability of bound ligand to activate the receptor
Partial Agonist
produce a medium response regardless of dose
Dose-Response Curve (DRC)
graph of the relationship between drug doses and effects
Pharmacodynamics
the functional relationship between drugs and their targets
Biotransformation
produces active metabolites that may produce side
effects.
Bioavailable
the extent a substance or drug becomes completely available to its intended biological destination(s) which varies with route of ingestion
Pharmacokinetics
factors that affect movement of a drug through the body
Blood-brain barrier
Tight junctions within the CNS prevent the movement of large molecules that can limit drug availability.
- Many drugs that might be useful are too
large to pass the blood-brain barrier to
enter the brain.
Drug Tolerance
Successive exposures have decreasing effects
Metabolic Tolerance
organ systems become more effective at eliminating the drug
Functional Tolerance
Target tissue may show altered sensitivity to the drug
Down- Regulation
is a reduction in the total number of receptors available to be stimulated due to prolonged receptor activation or fewer receptors available due to agonist drug
Up-Regulation
is a cell increase of receptors in response to an agonist
Cross-Tolerance
Tolerance to a whole class of chemically similar drugs
Withdrawal Symptoms
caused by drug tolerance
Sensitization
drug effects that become stronger with repeated treatment
