Introduction: Glutamate is the principal excitatory neurotransmitter in the mammalian brain, central to synaptic transmission, plasticity, and learning. B.Pharm students must understand glutamatergic pharmacology, including glutamate synthesis (glutaminase), vesicular loading (VGLUTs), clearance by EAAT transporters, and metabolism via the glutamate–glutamine cycle. Key receptor families—ionotropic NMDA, AMPA, kainate, and metabotropic mGluRs—mediate diverse signaling, calcium dynamics, and pathophysiology such as excitotoxicity in stroke, neurodegeneration, and epilepsy. Therapeutic agents (memantine, ketamine) target these pathways. This concise, keyword-rich overview links molecular mechanisms to clinical and pharmacological implications for B.Pharm training. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is the primary excitatory neurotransmitter in the central nervous system?
- GABA
- Acetylcholine
- Glutamate
- Dopamine
Correct Answer: Glutamate
Q2. Which enzyme converts glutamine into glutamate within neurons?
- Glutamine synthetase
- Glutaminase
- Glutamic acid decarboxylase (GAD)
- Monoamine oxidase (MAO)
Correct Answer: Glutaminase
Q3. Which protein is responsible for packaging glutamate into synaptic vesicles?
- EAAT2 (GLT-1)
- VGLUT (vesicular glutamate transporter)
- GAT (GABA transporter)
- VMAT (vesicular monoamine transporter)
Correct Answer: VGLUT (vesicular glutamate transporter)
Q4. High-affinity removal of extracellular glutamate is primarily mediated by which transporter family?
- VGAT transporters
- EAAT (excitatory amino acid transporters)
- VGLUT transporters
- Choline transporters
Correct Answer: EAAT (excitatory amino acid transporters)
Q5. Which glutamate receptor requires a co-agonist (glycine or D‑serine) for activation?
- AMPA receptor
- Kainate receptor
- NMDA receptor
- mGluR Group II
Correct Answer: NMDA receptor
Q6. The voltage-dependent magnesium block is a characteristic property of which receptor?
- AMPA receptor
- Nicotinic acetylcholine receptor
- NMDA receptor
- GABAA receptor
Correct Answer: NMDA receptor
Q7. Which AMPA receptor subunit editing (Q/R site) strongly influences calcium permeability?
- GluA1
- GluA2
- GluA3
- GluA4
Correct Answer: GluA2
Q8. Which clinically used drug is an NMDA receptor antagonist approved for moderate to severe Alzheimer’s disease?
- Memantine
- Phenytoin
- Donepezil
- Selegiline
Correct Answer: Memantine
Q9. Ketamine produces dissociative anesthesia primarily by blocking which receptor?
- GABAB receptor
- NMDA receptor
- AMPA receptor
- mGluR5 receptor
Correct Answer: NMDA receptor
Q10. Excitotoxic neuronal death following ischemia is mainly due to excessive influx of which ion through NMDA receptors?
- Sodium (Na+)
- Potassium (K+)
- Calcium (Ca2+)
- Chloride (Cl-)
Correct Answer: Calcium (Ca2+)
Q11. In the glutamate–glutamine cycle, which astrocytic enzyme converts glutamate to glutamine?
- Glutaminase
- Glutamine synthetase
- Glutamic acid decarboxylase (GAD)
- Glutamate dehydrogenase
Correct Answer: Glutamine synthetase
Q12. What is the main precursor supplied to neurons for synthesis of glutamate?
- Glucose
- Glutamine
- GABA
- Acetyl‑CoA
Correct Answer: Glutamine
Q13. Group I metabotropic glutamate receptors (mGluR1 and mGluR5) are coupled to which G protein and second-messenger pathway?
- Gs — cAMP increase
- Gi/o — inhibition of adenylyl cyclase
- Gq — phospholipase C with IP3/DAG signaling
- G12/13 — Rho activation
Correct Answer: Gq — phospholipase C with IP3/DAG signaling
Q14. Which EAAT subtype is the predominant astrocytic glutamate transporter in the adult forebrain?
- EAAT1 (GLAST)
- EAAT2 (GLT-1)
- EAAT3 (EAAC1)
- EAAT4
Correct Answer: EAAT2 (GLT-1)
Q15. Long-term potentiation (LTP) at hippocampal Schaffer collateral–CA1 synapses requires activation of which receptor?
- AMPA receptor only
- NMDA receptor
- GABAA receptor
- Kainate receptor only
Correct Answer: NMDA receptor
Q16. Which compound is a competitive antagonist at the glutamate binding site of NMDA receptors used in research?
- MK-801 (dizocilpine)
- AP5 (2‑amino‑5‑phosphonopentanoate)
- Memantine
- Ketamine
Correct Answer: AP5 (2‑amino‑5‑phosphonopentanoate)
Q17. Which glutamate receptor subtype mediates the fastest excitatory synaptic currents?
- NMDA receptors
- AMPA receptors
- mGluR Group I
- mGluR Group II
Correct Answer: AMPA receptors
Q18. Which gliotransmitter acts as a co-agonist at the NMDA receptor and is mainly released by astrocytes?
- Glycine
- D‑serine
- Glutamine
- GABA
Correct Answer: D‑serine
Q19. Acute ischemic stroke causes neuronal injury primarily through which glutamatergic mechanism?
- Reduced glutamate release causing synaptic failure
- Excessive glutamate release and excitotoxicity
- Autoimmune attack on glutamate receptors
- Excessive GABAergic inhibition
Correct Answer: Excessive glutamate release and excitotoxicity
Q20. Which enzyme converts glutamate into GABA in GABAergic neurons?
- Glutaminase
- Glutamic acid decarboxylase (GAD)
- Glutamine synthetase
- Glutamate dehydrogenase
Correct Answer: Glutamic acid decarboxylase (GAD)
Q21. RNA editing of the GluA2 AMPA subunit Q/R site is catalyzed by which enzyme?
- ADAR1
- ADAR2
- RNase H
- Dicer
Correct Answer: ADAR2
Q22. Which NMDA receptor subunit is obligatory for formation of functional NMDA receptors?
- NR2A
- NR2B
- NR1
- NR3
Correct Answer: NR1
Q23. MK‑801 (dizocilpine) blocks NMDA receptors by which mechanism?
- Competitive antagonist at glutamate binding site
- Noncompetitive open‑channel blocker
- Positive allosteric modulator
- Glycine site agonist
Correct Answer: Noncompetitive open‑channel blocker
Q24. Activation of extrasynaptic NMDA receptors is more strongly associated with which outcome compared to synaptic NMDA activation?
- Enhanced synaptic plasticity and survival signaling
- Neuroprotection and CREB activation
- Cell death signaling and CREB shutoff
- Promotion of long‑term potentiation only
Correct Answer: Cell death signaling and CREB shutoff
Q25. Which VGLUT isoform is predominantly expressed in cortex and hippocampus and associated with glutamatergic neurons?
- VGLUT1
- VGLUT2
- VGLUT3
- EAAT2
Correct Answer: VGLUT1
Q26. Kainate receptors differ from AMPA receptors in that kainate receptors often exert which type of effect?
- Only postsynaptic fast excitation
- Only slow metabotropic inhibition
- Both pre‑ and postsynaptic modulation of neurotransmitter release
- Exclusive activation of Gs signaling
Correct Answer: Both pre‑ and postsynaptic modulation of neurotransmitter release
Q27. Memantine’s therapeutic action in Alzheimer’s disease is best described as which mechanism at NMDA receptors?
- High‑affinity competitive antagonist
- Low‑affinity uncompetitive (open‑channel) blocker
- Full agonist at the glycine site
- Positive allosteric modulator
Correct Answer: Low‑affinity uncompetitive (open‑channel) blocker
Q28. Which EAAT subtype is primarily neuronal and expressed at neuronal plasma membranes?
- EAAT1 (GLAST)
- EAAT2 (GLT-1)
- EAAT3 (EAAC1)
- EAAT5
Correct Answer: EAAT3 (EAAC1)
Q29. Activation of Group I mGluRs increases which intracellular second messenger leading to calcium release from stores?
- cAMP
- IP3 (inositol trisphosphate)
- cGMP
- ATP
Correct Answer: IP3 (inositol trisphosphate)
Q30. Reduced expression or function of the astrocytic glutamate transporter EAAT2 (GLT‑1) has been implicated in which neurodegenerative disease?
- Alzheimer’s disease
- Amyotrophic lateral sclerosis (ALS)
- Huntington’s disease
- Multiple sclerosis
Correct Answer: Amyotrophic lateral sclerosis (ALS)
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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