psyc 211- Drugs

Where does our knowledge of neurotransmitters signaling come from

• It comes from studying the venom of many species

• Many of these compounds interfere with neurotransmitter signaling at the neuromuscular junction, which can cause paralysis (no movement) or spasms (excessive muscle contraction)

What is Acetylcholine

• it is a neuromodulator in the brain and spinal cord, often acting at axoaxonic synpapses

• It is also used by neurons outside the brain

• Motor neurons generally release acetylcholine as their main neurotransmitters

• Sensory neurons generally release glutamate as their main neurotransmitter

What is black widow spider venom

• It is poison produced by the black widow spider that triggers the realse of acetylcholine from motor neurons

What is botulinum toxin

• Botox

• It is toxin produced by the bacteria that grow in improperly canned food. It prevents acetylcholine release from motor neurons, causing muscle paralysis

• In high doses, it could kill

What is neostigime

• it is a drug that inhibits acetylcholinesterase, the enzyme that breaks down acetylcholine in the synapse

• Neostigmine causes acetylcholine to stay around longer in the synapse, strengthening and prolonging muscle contraction

What is the Myasthenia Gravis disorder

• it is an autoimmune disorder where a person’s immune system attacks healthy acetylcholine receptors

• People with this disorder become progressively weaker and weaker over time

• There is still no good way to stop the immune system from doing this or a way to restore healthy acetylcholine receptors, but drugs like neostigimine can reduce fatiguability by keeping acetylcholine in the synapse longer

How are drugs categorized

• a common way to classify drugs relates to how they affect post synaptic receptor activity

• A receptor agonist is a drug that increases the activity of postsynaptic receptors

• A receptor antagonist is a drug that decreases the activity of postsynaptic receptors

How do drugs affect the activity of postsynaptic receptors

• direct agonists/ antagonists bind directly to postsynaptic receptors

• Indirect agonists/ antagonists affect the activity of postsynaptic receptors in an indirect manner (i.e. They do not directly bind to postsynaptic receptors)

What is psychosis

• It is a condition of the mind that results in difficulties determining what is real and what is not real

• Symptoms may include delusions,hallucinations,incoherent speech ,and behaviour that is inappropriate for the situation

What are antipsychotics (dopamine receptor blockers)

• it is the class of druges used to treat psychosis

• they are mostly dirty drugs, which means that they bind to more than one receptor

• They all directly block the dopamine D2 receptor, which is an inhibitory ,metabotropic receptor expressed by neurons all over the brain

What is the serotion in 2A receptor (serotonin receptor activators)

• It is a part of the brain that is activated by a wide variety of drugs that cause hallucinations

• The serotonin 2A receptor (5-HT2A) is metabotropic, and is expressed by neurons all over the brain. In some cells it is excitatory, while in other cells it is inhibitory

• Although, not all agonists of the serotonin 2A receptor causes hallucinations

The see

What are the 4 drugs that directly activate the serotonin 2A receptor

• Hallucinogens: mescaline, psilocybin, LSD

• Not hallucinogens: lisuride

• When these drugs activate the 5HT-2A receptor, they launch an intracellular signaling cascade that starts with the protein G q/11.

• Serotonin activates this receptor in the same manner

• Hallucinogenic drugs also trigger the receptor to activate the G i/10 protein

• Hallucinations seem to be the result of this receptor activating the G i/10 protein

What is biased agomism

• it is when a ligand causes a metabotropic receptor to preferentially activate one type of intracellular G protein, whereas another ligand at the same receptor might preferentially activate a different G protein

• It all relates to how the ligand binds to the receptor

What is competitive binding

• direct agonists/ antagonists can be classified as competitive or non-competitive

• A competitive agonist acts similarly to the endogenous neurotransmitter. It activates the receptor by binding where the neurotransmitter normally binds. It can be full of partial agonists

• 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 is affinity

It refers to the probability and tightness of ligand-receptor binding

What is non-competitive binding

• It is when a drug binds to a receptor at a site that does not interfere with the binding site of the normal ligand

• It is possible for a neurotransmitter to bind to one site on a receptor while a drug binds to another site on the same receptor

• A non-competitive agonist fully or partially activates the receptor

• A non competitive antagonist fully blocks receptor activation. It doesn’t compete for the neurotransmitter binding site. It wins without competing by binding to an alternative site

What are allosteric modulators

• they are non competitive drugs that only influence receptor activity when the neurotransmitter is also bound to the receptor

• Negative allosteric modulators reduce the effect of the primary ligand

• Positive allosteric modulators amplify the effect of the primary ligand

What is Parkinson’s disease and what it it’s cause

• it is a neurological disorder that is 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 used as a drug to treat this disease becuas it increases dopamine production I mythe brain and acts as an indirect dopamine receptor agonit

Principles of pharmacology

• conventional neurotransmitters are made in axon terminals, where an enzyme converts a precursor molecule into a neurotransmitter

• Enzymes synthesize neurotransmitters from precursor molecules

• Once made, neurotransmitters are packaged into synaptic vesicles

• Many proteins in the axon terminal regulate neurotransmitter release (i.e. the vesicular release machinery)

• The clearance of neurotransmitters from the synapse is controlled the reuptake transporters proteins and enzymatic deactivation

What are methylphenidate and cocaine

• they are drugs that block catecholamine reuptake transporters, meaning that they block the reuptake of dopamine & norepinephrine

What are adderall and crystal meth

• they are drugs that reverse catecholamine reuptake transporters, causing dopamine and norepinephrine to flow out of the axon terminal before being packaged into a vesicle (i.e. action potential-independent, non-vesicular release)

• Ecstasy has a similar effect on all the monoamine reuptake transporters (i.e. causing the, to run backwards)

What are the categories of drugs

• according to their effects on postsynaptic receptor activity

• According to their behavioural effects (stimulant, depressant)

• According to their physiological effects (action potential blocker)

• According to their actions on specific proteins (serotonin reuptake blokcer)

How do heroin, morphine, and Imodium anti-diarrheal enter the brain

• heroin easily crosses the blood-brain barrier because an enzyme in the blood makes it very lipid/ fat soluble

• Morphine less easily crosses the blood barrier because it is less soluble in lipids than heroin

• Imodium anti-diarrheal do not cross the blood-brain barrier

• These opioid receptors all are inhibitory metabotropic receptors found throughout the body and brain. They get activated by endogenous opioid peptides that function as hormones in the body and as neuropeptides in the brain

What is tolerance

Era me

• it is when a drug effect gets smaller with repeated administration

• The body becomes used to the drug and actively counteracts its effects

• Ex: heroin

What is sensitization

• it occurs when a drug effect becomes larger with repeated use

• Ex: rodents sensitize the effects of cocaine and amphetamine