32 - Drugs affecting synaptic transmission in the CNS

Vocabulary-style flashcards covering key concepts, terms, and mechanisms from the lecture notes.

Presynaptic

Relating to the neuron terminal that releases neurotransmitter into the synaptic cleft.

Postsynaptic

Relating to the neuron or cell that possesses receptors for the transmitter.

Axon

Long projection of a neuron that conducts action potentials away from the cell body.

Axon terminal

End of the axon where vesicles fuse and release transmitter.

Vesicle

Membrane-bound sac storing neurotransmitter in the presynaptic terminal.

Transmitter (neurotransmitter)

Chemical that carries signal across the synapse.

Receptor

Protein on the postsynaptic membrane that binds transmitter to elicit a response.

Myelin sheath

Insulating layer around axons that increases conduction velocity.

Node of Ranvier

Gaps in myelin with high density of ion channels for saltatory conduction.

Biosynthesis

Formation of neurotransmitters inside the neuron.

Vesicular loading

Packaging transmitter into synaptic vesicles before release.

Synthetic enzymes

Enzymes that synthesize neurotransmitters.

Action potential propagation

Spread of the electrical impulse along the axon via Na+ influx.

Na+

Sodium ion involved in depolarization and action potential propagation.

Neurotransmitter release

Exocytotic release of transmitter into the synaptic cleft triggered by Ca2+.

Ca2+

Calcium ion that triggers vesicle fusion and transmitter release.

Receptor coupling

Linkage of receptor activation to intracellular signaling pathways.

Postsynaptic effect

Response produced in the postsynaptic cell after receptor activation.

Signal termination

Processes that end neurotransmission: reuptake, metabolism, breakdown.

Re-uptake

Transport of transmitter back into the presynaptic neuron for reuse or degradation.

Metabolism

Biochemical inactivation/alteration of a transmitter.

Enzymatic breakdown

Enzymatic degradation of transmitter in the synaptic cleft.

Blood-brain barrier

Selective barrier separating blood from brain tissue, limiting drug entry.

Lipids soluble

Ability of a compound to dissolve in fat; aids crossing the BBB.

Unionised

Non-ionized form of a molecule; more lipid-soluble, crosses membranes more easily.

L-DOPA

Dopamine precursor used to replenish brain dopamine.

Parkinson’s disease

Neurodegenerative disorder with dopamine deficit in nigrostriatal pathway.

Replacement therapy

Using a precursor or other means to substitute for deficient transmitter.

Direct agonism

Drugs that activate receptors directly without a transmitter.

Reuptake inhibition

Blockade of transmitter reuptake to increase synaptic transmitter levels.

Degradative enzyme inhibition

Inhibition of enzymes that break down transmitter to raise its levels.

D2 receptor antagonists

Block D2 dopamine receptors; used as antipsychotics.

Antipsychotic (neuroleptic)

Drug that treats psychosis, often via D2 receptor blockade.

Haloperidol

Typical antipsychotic; D2 receptor antagonist.

Metoclopramide

D2 antagonist; antiemetic and antipsychotic uses.

Chlorpromazine

Phenothiazine antipsychotic; D2 receptor antagonist.

Benztropine

Muscarinic acetylcholine receptor antagonist used in Parkinsonian symptoms.

5-HT3 antagonists

Block 5-HT3 receptors; antiemetics.

Ondansetron

5-HT3 receptor antagonist used as antiemetic.

D1 receptor selective agonist

Drug that preferentially activates D1 receptors (example given: bromocriptine).

Bromocriptine

Dopamine receptor agonist (not purely D1 selective in practice; noted as D-1 agonist example in the notes).

Opioid mu receptor agonists

Activate mu-opioid receptors to produce analgesia.

Morphine

Classic mu-opioid receptor agonist and analgesic.

5-HT1A agonists

Activate 5-HT1A receptors; can have anxiolytic effects.

Buspirone

Partial 5-HT1A agonist with anxiolytic action.

Allosteric modulators

Molecules that bind to a receptor at a site distinct from the active site to modulate activity.

GABAA receptors

Ionotropic GABA receptors that form chloride channels to inhibit neurons.

Benzodiazepines

Positive allosteric modulators of GABAA receptors; sedative, anxiolytic, anticonvulsant.

Diazepam

A benzodiazepine with anxiolytic/sedative properties.

Barbiturates

Barbiturate class; act as GABAergic modulators with sedative/anticonvulsant effects.

Phenobarbitone

Barbiturate; enhances GABAergic inhibition.

GABA uptake blocker

Inhibits GABA reuptake to increase synaptic GABA.

Tiagabine

GABA uptake inhibitor; anticonvulsant.

Dopamine uptake inhibitor

Blocks dopamine transporter to increase synaptic dopamine.

Nomifensine

Dopamine/NE uptake inhibitor with antidepressant effects.

Monoamine oxidase inhibitors

Inhibit MAO enzymes to prevent breakdown of monoamines.

Phenelzine

Non-selective MAO inhibitor used as antidepressant.

MAO-B inhibitor

Selective MAO-B inhibitor to raise brain dopamine levels.

Selegiline

MAO-B inhibitor used in Parkinson’s and depression.

GABA transaminase inhibitor

Inhibits GABA transaminase to raise GABA levels.

Vigabatrin

GABA transaminase inhibitor; anticonvulsant.

Autoreceptor-mediated feedback inhibition

Autoreceptors regulate transmitter release via feedback; antagonism can enhance transmission.

Mianserin

Antidepressant with alpha-2 adrenergic (A2) antagonist properties.

A2 antagonist properties

Antagonism at alpha-2 adrenergic autoreceptors increasing transmitter release.

Monoamine Theory of Depression

Idea that depression is due to hypoactivity at monoaminergic synapses.

Schildkraut

Proposed the Monoamine Theory of Depression (1965).

Depression (clinical strategies)

Approaches to enhance monoaminergic transmission: reuptake inhibition, MAO inhibition, autoreceptor antagonism.

Epilepsy

Neurological disorder treated by drugs that reduce neuronal excitability.

Na+ channel blocker

Block Na+ channels to reduce action potential propagation; anticonvulsant use.

Phenytoin

Na+ channel blocker used as anticonvulsant.

Carbamazepine

Na+ channel blocker used as anticonvulsant.

Ca2+ channel blocker

Block voltage-gated Ca2+ channels to reduce transmitter release.

Ethosuximide

Ca2+ channel blocker effective for absence seizures.

GABAA receptor positive allosteric modulation

Enhance GABAergic inhibition via allosteric sites (e.g., benzodiazepines, barbiturates).

GABA reuptake inhibition

Block GABA reuptake to elevate synaptic GABA (e.g., tiagabine).

GABA degradative enzyme inhibition

Inhibit enzymes that break down GABA to raise GABA levels (e.g., vigabatrin).

Acetylcholinesterase inhibitors

Block acetylcholinesterase to increase acetylcholine in CNS/PNS (Alzheimer’s).

Donepezil

AChE inhibitor used to treat Alzheimer's disease.

Rivastigmine

AChE inhibitor used for Alzheimer’s disease.

Galantamine

AChE inhibitor used for Alzheimer’s disease.

Alzheimer’s disease

Neurodegenerative disease with loss of acetylcholine and cognitive decline.