Lecture 8 Flashcards
Psychosis
1% of people
Schizophrenea
Was treated by asylums
Cost a lot so conditions dropped rapidly
Became horrible
Moved to outpatient care when antipsychotics came along
Now usually short term treatment as inpatients and care in community
Antipsychotics
Directly block the D2 dopamine receptor which is an inhibitory metabotropic receptor 1st gen (typical) were specific to D2 but had too many sides 2nd gen (atypical) are less specific to d2 and have less sides
Dirty drugs
Bind to many receptors
Direct serotonin receptor agonists
Recreational use as hallucinogens
Directly activate serotonin 2A receptors - inhibitory metabotropic receptors
BUT not all serotonin 2A receptor activation cases hallucinations
Hallucinogens
Mescaline, psilocybin and LSD bind to the serotonin 2a receptor and cause a signaling cascade that starts with G q/11
Serotonin usually does this too
BUT these three also activate the receptor in a way that stimulates Gi/o and causes hallucinations/ This action by the 5HT2A induced activation is what causes them
Lisuride is a treatment tfo migrated that also does not activate Gi/o
Biased Agonism
When a metabotropic receptor ligands causes the receptor to preferentially activate one type of intracellular g protein whereas another ligand preferentially activates another by binding to the same receptor.
Sasha Shulgin
Made many psychoactive drugs
Useful because you cannot test these on animals as they cannot tell you the results and it is unethical to use humans
He wrote a lot of books about this stuff and illegal drugs he created flooded the market after he made them
Drugs can affect postsynaptic receptor activity directly or indirectly
Direct agonist/antagonist - bind to the receptor and exert an effect
Indirect agonist/antagonist - the proteins they bind to are not postsynaptic receptors but they still have an effect here
Postsynaptic agonist = increase activity of postsynaptic receptor. Antagonists decrease it
We classify drugs based on
their effects on the postsynaptic receptor activity
Competitive agonists
Chemical level context
Act similarly to the endogenous neurotransmitter
Binds where this usually binds
Can be full or partial agonists
Full = like normal
CONTEXT
If your brain is full of serotonin, a full serotonin receptor agonist would not do much - same as normal
BUT
in this situation, if you had a partial agonist there would be less activation. In this individual it would be a partial antagonist
If the person had little serotonin at baseline, it would increase activity and hence be a partial agonist
What determines the competition for a receptor site between a neurotransmitter and an exogenous drug?
Affinity and relative concentration
Non-competitive binding
Drug binds to a site that does not interfere with the site used by the principle ligand
3 types of non-competitive drug
Non-competitive agonist, fully or partially activates the receptor
Non-competitive antagonist foully blocks receptor activation. It does not compete, it wins without competing
Allosteric modulators: Non-competitive drugs that only influence activity when the neurotransmitter is bound to the receptor
Negative allosteric modulators reduce the effect of primary ligands
Positive allosteric modulators increase them
Do yo need to bind to a receptor to influence their effects?
No. Many drugs influence the activity of post-synaptic receptors without binding to them
Parkinsons
Due to atrophy of dopaminergic neurons
Give L dopa as it passes BBB and is only taken up by dopaminergic neurons because they think its dopamine (via dopamine reuptake protein)
Does not have effects in the body as not dopamine. Endocrine cells do not take it up as they take back very little of the dopamine they release (it should all be carried away via the blood) so no large drop in BP
Is then changed into dopamine in the cytoplasm and results in an increased secretion of dopamine therefore is a dopamine post synaptic receptor agonist
Titrate dose up as neurons die off. Eventually stops working but minimizes symptoms well for years
