Test 2 Flashcards
What is an antipsychotic?
class of drugs used to treat psychosis - They are mostly dirty drugs, which means they bind to more than one type of receptor, but the one action they all have in common is they directly block the dopamine D2 receptor (direct dopamine receptor antagonsists)
What are atypical antopsychotics?
bind to a lot of receptors and changes the activity of receptors in different ways
- Didn’t completely cure psychosis; there were side effects
What is psychosis?
an abnormal condition of the mind that results in difficulties determining what is real and what isn’t
- Affects around 1% of the population
- Symptoms may include delusions, hallucinations, incoherent speech, and behaviour that is inappropriate for the situation
What are direct serotonin receptor agonists (receptor activators)?
- Used recreationally to cause hallucinations
- Activate serotonin 2A receptors, which are inhibitory metabotropic receptors expressed by neurons all over the brain
- But other direct serotonin 2A receptor agonists do not cause hallucinations at all
- For a long time, people did not understand why some 5HT-2A receptor agonists caused massive hallucinations while others did nothing of the sort
What is biased agonism?
• When a metabotropic receptor ligand causes the receptor to preferentially activate one type of intracellular g protein, whereas another ligand at the same receptor might preferentially activate a different g protein
- Different ligands binding to each receptor
What are direct agonists/antagonists?
drugs that affect postsynaptic receptor activity by directly binding to postsynaptic receptors
What are indirect agonists/antagonists?
drugs that affect postsynaptic activity in an indirect manner; the proteins they bind to are not postsynaptic receptors
What is a receptor agonist?
drug that directly or indirectly increases the activity of postsynaptic receptor proteins
What are drugs?
exogenous chemicals that at low doses significantly alter the function of certain cells
What is a competitive agonist?
acts similarly to the endogenous NT; it activates the receptor by binding where the neurotransmitter normally binds
What is a competitive antagonist?
attaches to the same binding where the neurotransmitter normally binds, but it doesn’t activate the receptor
- Competitive antagonists are full antagonists
What will the competition for a binding site between an endogenous NT and an exogenous drug will depend on?
their relative concentrations and their affinity for the binding site
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’s possible for a NT to bind on one site of a receptor while a drug binds on another
What is a non-competitive agonist?
it fully or partially activates the receptor
What is a non-competitive antagonist?
fully blocks receptor activation; it doesn’t compete for the NT binding site
- It “wins” without competing by binding to an alternative site
What are allosteric modulators?
non-competitive drugs that only influence receptor activity when the NT is also bound to the receptor
What are negative allosteric modulators?
reduce the effect of the primary ligand
What are positive allosteric modulators?
amplify the effect of the primary ligand
What is Parkinson’s disease?
a neurological disorder that is characterized by tremors, rigidity of limbs, poor balance, and difficulty initiating movements
- It’s caused by the degeneration (death) of dopamine neurons in the midbrain
How is dopamine made?
Made from tyrosine –> (enzyme) –> L-DOPA –> (enzyme) –> dopamine
How are conventional NTs made?
made in axon terminals and are made from precursor molecules (generally from amino acids)
- In some cases, precursor molecules can be administered as drugs since they can increase the amount of NT that is made and released precursors act as receptor agonists
What is the synthesis of NT form precursor molecules is controlled by ?
Enzymes
- Some antagonists work by blocking these enzymes, thus reducing production of the NT so there is less in each vesicle
What is the clearance of NTs from the synapse is controlled by?
reuptake transporter proteins and enzymatic deactivation
What is the therapeutic index?
the ratio between the dose that produces desired effect in 50% of animals and the dose that produces toxic effects in 50% of animals