Pharmacodynamics: GABA, Glutamate, and Other Neurotransmitters

A collection of vocabulary flashcards covering the pharmacodynamics, receptor types, biosynthetic pathways, and pharmacology of GABA, glutamate, dopamine, and serotonin.

Glutamate

The main excitatory neurotransmitter in the brain and spinal cord, mediating approximately $75\%$ of central nervous system excitatory transmission and released via $Ca^{2+}$-dependent exocytosis.

NMDA Receptor

A fast ionotropic glutamate receptor that requires glycine for activation and permits $Ca^{2+}$ entry upon channel opening.

AMPA Receptor

A fast ionotropic ligand-gated ion channel receptor activated by glutamate that allows $Na^+$ influx and $K^+$ efflux.

Kainate Receptor

An ionotropic glutamate receptor that mediates fast excitatory synaptic responses.

Glutamate Decarboxylase (GAD)

The enzyme that catalyzes the decarboxylation of glutamate to synthesize GABA.

Vesicular GABA Transporter (VGAT)

The transporter protein responsible for concentrating synthesized GABA into presynaptic synaptic vesicles.

GABA Transaminase (GABA-T)

The primary metabolic enzyme that degrades GABA by transamination to succinic semialdehyde, which is subsequently converted to succinate.

$GABA_A$ Receptor

A pentameric ionotropic receptor, most commonly composed of $2\alpha$, $2\beta$, and $1\gamma$ subunits, that conducts fast inhibitory $Cl^-$ influx upon the binding of two GABA molecules.

$GABA_B$ Receptor

A metabotropic G-protein-coupled receptor that mediates slow presynaptic and postsynaptic inhibition by coupling to $G_i$ (inhibiting adenylyl cyclase to open $K^+$ channels) and $G_o$ (inhibiting $Ca^{2+}$ influx).

Benzodiazepines

A drug class (including diazepam, alprazolam, and lorazepam) that binds to the $\alpha$ subunit of $GABA_A$ receptors to increase the frequency of $Cl^-$ channel opening.

Barbiturates

A drug class (such as phenobarbital and pentobarbital) that binds to $GABA_A$ receptors at a distinct site to increase the duration of $Cl^-$ channel opening while suppressing AMPA-mediated excitation.

Z-drugs

Hypnotic medications (e.g., zolpidem, zaleplon, eszopiclone) that selectively bind the $\alpha_1$ subunit of the $GABA_A$ receptor to treat short-term insomnia.

Baclofen

A $GABA_B$ receptor agonist that opens $K^+$ channels and reduces $Ca^{2+}$ influx, used clinically to relieve muscle spasticity in multiple sclerosis or spinal cord injury.

Tiagabine

A GABA reuptake inhibitor that blocks the GAT-1 transporter to increase synaptic GABA levels, used as an adjunct in epilepsy.

Tyrosine Hydroxylase

The rate-limiting enzyme in dopamine synthesis that converts the amino acid tyrosine into L-DOPA.

Dopamine Transporter (DAT)

A presynaptic membrane protein that clears dopamine from the synaptic cleft back into the presynaptic neuron for recycling or degradation.

Homovanillic Acid (HVA)

The primary metabolic breakdown product of dopamine produced via catechol-O-methyltransferase (COMT), measurable in blood and urine as a marker of dopamine activity.

Nigrostriatal Pathway

A dopaminergic pathway originating in the substantia nigra and projecting to the striatum that controls motor function and degenerates in Parkinson's disease.

Mesolimbic Pathway

A dopaminergic pathway originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens and limbic system, governing reward and motivation.

Mesocortical Pathway

A dopaminergic tract connecting the ventral tegmental area (VTA) to the prefrontal cortex that regulates cognition and working memory.

Tuberoinfundibular Pathway

A dopaminergic pathway connecting the hypothalamus to the pituitary gland that inhibits prolactin release; its blockade causes hyperprolactinemia.

$D_1$-like Receptors

A family of dopamine GPCRs ($D_1$ and $D_5$) that couple to stimulatory G-proteins ($G_s$) to activate adenylyl cyclase, increase cAMP, and produce excitatory effects.

$D_2$-like Receptors

A family of dopamine GPCRs ($D_2$, $D_3$, and $D_4$) that couple to inhibitory G-proteins ($G_i$) to decrease cAMP production, producing inhibitory effects.

$D_3$ Receptor

A $D_2$-like dopamine receptor localized predominantly to the nucleus accumbens and limbic structures, corresponding to its role in reward processes.

$D_4$ Receptor

A $D_2$-like dopamine receptor subtype with high affinity for atypical antipsychotics like clozapine, relevant in treatment-resistant schizophrenia.

Levodopa

A dopamine precursor that crosses the blood-brain barrier to be converted into dopamine, administered with carbidopa to prevent peripheral breakdown.

Amantadine

An antiparkinsonian and antiviral agent that enhances dopamine release, reduces dopamine reuptake, and acts as an NMDA receptor antagonist.

Enterochromaffin Cells

Specialized cells in the gastrointestinal tract that produce approximately $90\text{--}95\%$ of the body's serotonin to regulate gut motility and secretion.

Raphe Nuclei

Brainstem structures containing serotonergic cell bodies that account for approximately $5\text{--}10\%$ of total body serotonin and project throughout the central nervous system.

Tryptophan Hydroxylase

The enzyme that converts dietary tryptophan into 5-hydroxytryptophan (5-HTP) during the first step of serotonin synthesis.

Serotonin Transporter (SERT)

The transporter responsible for the reuptake of released serotonin from the synaptic cleft into presynaptic neurons and platelets.

5-Hydroxyindoleacetic Acid (5-HIAA)

The principal urinary breakdown metabolite of serotonin produced via monoamine oxidase A (MAO-A), used as a diagnostic biomarker for carcinoid tumors.

$5\text{-HT}_1$ Receptors

Serotonin GPCR subtypes ($5\text{-HT}_{1\text{A}\text{--}\text{F}}$) coupled to $G_i$ that decrease cAMP levels, targeted by triptans and buspirone.

$5\text{-HT}_2$ Receptors

Serotonin GPCR subtypes ($5\text{-HT}_{2\text{A}\text{--}\text{C}}$) coupled to $G_q$ that increase intracellular $Ca^{2+}$, modulating mood, psychosis, and platelet aggregation.

$5\text{-HT}_3$ Receptor

The only ligand-gated ionotropic serotonin receptor ($Na^+/K^+$ channel), which mediates the vomiting reflex and is antagonized by ondansetron.

Selective Serotonin Reuptake Inhibitors (SSRIs)

A drug class (including fluoxetine and sertraline) that blocks SERT to elevate synaptic serotonin concentrations for the treatment of depression and anxiety.

Tricyclic Antidepressants (TCAs)

A second-line antidepressant drug class (including imipramine and amitriptyline) that blocks the reuptake of both serotonin (5-HT) and norepinephrine (NE).

Triptans

Receptor-specific $5\text{-HT}_{1\text{B}/1\text{D}}$ agonists utilized clinically for the acute treatment of migraine headaches.