Transporters, Receptors, and Enzymes as Targets of Psychopharmacological Drug Action

Question 1

Role of Transporters

Answer 1

Transporters are proteins that move neurotransmitters across cell membranes. They play a crucial role in the reuptake of neurotransmitters back into presynaptic neurons after they have been released into the synaptic cleft.

Question 2

SERT (Serotonin Transporter)

Answer 2

Removes serotonin from the synapse. Targeted by SSRIs (e.g., fluoxetine) to block reuptake and increase serotonin levels.
Part of monoamine transporter family.

Question 3

DAT (Dopamine Transporter)

Answer 3

Removes dopamine from the synapse. Targeted by drugs like cocaine and certain ADHD medications (e.g., methylphenidate) to increase dopamine levels.
Part of monoamine transporter family.

Question 4

NET (Norepinephrine Transporter)

Answer 4

Clears norepinephrine from the synapse. Drugs like SNRIs (e.g., venlafaxine) inhibit this transporter to increase norepinephrine availability.
Part of monoamine transporter family.

Question 5

Ionotropic Receptors

Answer 5

Ligand-gated ion channels that allow ions to pass through the membrane when activated by a neurotransmitter. They mediate rapid synaptic transmission (e.g., NMDA receptors for glutamate)

Question 6

Metabotropic Receptors

Answer 6

G-protein-coupled receptors (GPCRs) that activate intracellular signaling pathways rather than directly controlling ion flow. They have slower but longer-lasting effects (e.g., dopamine D2 receptors)

Question 7

Partial Agonists

Answer 7

Drugs that partially activate receptors but do not elicit the full effect, often used to balance neurotransmission (e.g., aripiprazole as a dopamine partial agonist)
In the presence of a full agonist, the partial agonist will actually turn down the strength of various downstream signals = stabilizers

Question 8

Full Agonist

Answer 8

Causes conformational changes that lead to max signal transduction → all downstream effects of signal transduction (phosphorylation of proteins and gene activation) are maximized

Question 9

Inverse agonist

Answer 9

Opposite action compared to agonist; produce conformational change in G-protein-linked receptor that renders it inactive, even constitutive activity is blocked

Question 10

No agonist

Answer 10

Synonymous with constitutive activity; low level activity on GPCR

Question 11

Enzyme activity

Answer 11

conversion of one molecule into another

Question 12

Irreversible enzyme inhibitor

Answer 12

The binding is locked so permanently that such irreversible enzyme inhibition is sometimes called the work of a “suicide inhibitor,” since the enzyme essentially commits suicide by binding to the irreversible inhibitor

Question 13

Reversible enzyme inhibitor

Answer 13

can be challenged by a competing substrate for the same enzyme. In the case of a reversible inhibitor, the molecular properties of the substrate are such that it can get rid of the reversible inhibitor

Question 14

Enzymes in Neurotransmitter Metabolism

Answer 14

Enzymes are responsible for breaking down neurotransmitters and terminating their action

Question 15

Monoamine Oxidase (MAO)

Answer 15

Breaks down monoamines like serotonin, norepinephrine, and dopamine. MAO inhibitors (e.g., phenelzine) block this enzyme, increasing the levels of these neurotransmitters

Question 16

Acetylcholinesterase

Answer 16

Breaks down acetylcholine in the synaptic cleft. Inhibitors like donepezil increase acetylcholine levels and are used in treating Alzheimer’s disease.

Question 17

Cytochrome P450 (CYP450)

Answer 17

Most psychotropic drugs also target the CYP450 drug metabolizing enzymes either as a substrate, inhibitor, and/or inducer. CYP450 enzymes in the gut wall or liver convert the drug substrate into a biotransformed product in the bloodstream. After passing through the gut wall and liver, the drug will exist partially as unchanged drug and partially as biotransformed product in the bloodstream.

Question 18

CYP1A2 Inhibitors

Answer 18

Inhibitors slow down the activity of CYP enzymes, leading to increased blood levels of drugs metabolized by these enzymes. Fluvoxamine (SSRI)
Ciprofloxacin (antibiotic)
Cimetidine (H2 blocker for acid reflux)

Question 19

CYP2D6 Inhibitors

Answer 19

Inhibitors slow down the activity of CYP enzymes, leading to increased blood levels of drugs metabolized by these enzymes.
Fluoxetine (SSRI)
Paroxetine (SSRI)
Bupropion (antidepressant)
Quinidine (antiarrhythmic)

Question 20

CYP3A4 Inhibitors

Answer 20

Inhibitors slow down the activity of CYP enzymes, leading to increased blood levels of drugs metabolized by these enzymes.
Ketoconazole (antifungal)
Erythromycin (antibiotic)
Clarithromycin (antibiotic)
Grapefruit juice (can significantly inhibit CYP3A4 in the gut)

Question 21

CYP2C19 Inhibitors

Answer 21

Inhibitors slow down the activity of CYP enzymes, leading to increased blood levels of drugs metabolized by these enzymes.
Omeprazole (proton pump inhibitor)
Fluoxetine (SSRI)
Fluvoxamine (SSRI)

Question 22

CYP1A2 Inducers

Answer 22

Inducers increase the activity of CYP enzymes, leading to faster metabolism of drugs, potentially reducing their effectiveness.
Smoking (polycyclic aromatic hydrocarbons in cigarette smoke)
Rifampin (antibiotic)
Carbamazepine (anticonvulsant, mood stabilizer)

Question 23

CYP3A4 Inducers

Answer 23

Inducers increase the activity of CYP enzymes, leading to faster metabolism of drugs, potentially reducing their effectiveness
Carbamazepine (anticonvulsant, mood stabilizer)
Phenytoin (anticonvulsant)
Rifampin (antibiotic)
St. John’s Wort (herbal antidepressant)
Phenobarbital (barbiturate)

Question 24

CYP2C19 Inducers

Answer 24

Inducers increase the activity of CYP enzymes, leading to faster metabolism of drugs, potentially reducing their effectiveness
Carbamazepine (anticonvulsant, mood stabilizer)
Rifampin (antibiotic)
Phenobarbital (barbiturate)