STAHL'S ESSENTIAL PSYCHOPHARMACOLOGY
NEUROSCIENTIFIC BASIS AND PRACTICAL
APPLICATIONS
5TH EDITION
AUTHOR(S)STEPHEN M. STAHL
TEST BANK
1
Reference
Ch. 1 — Chemical Neurotransmission — Monoamine synthesis,
vesicular storage, and release
Stem
A 62-year-old patient with late-onset depressive symptoms and
orthostatic hypotension is being considered for an
antidepressant. The patient’s chart notes prior sensitivity to
drugs that increase synaptic monoamines and long-standing
hypertension controlled on an α-1 blocker. Which
pharmacologic approach best minimizes further orthostatic risk
while increasing synaptic monoamine tone through presynaptic
mechanisms?
,A. Inhibit monoamine oxidase A (MAO-A) to reduce monoamine
breakdown.
B. Block reuptake transporters (NET and SERT) to increase
synaptic monoamines.
C. Inhibit vesicular monoamine transporter (VMAT) to reduce
vesicular storage.
D. Use a drug that antagonizes presynaptic α-2 autoreceptors to
enhance release.
Correct answer
D
Rationales
Correct (D) — Antagonizing presynaptic α-2 autoreceptors
disinhibits transmitter release, increasing synaptic monoamines
(noradrenaline/serotonin) via enhanced exocytosis without
directly blocking peripheral α-1 receptors or causing
accumulation from inhibited breakdown. Stahl explains
presynaptic autoreceptor blockade as a mechanism to increase
release, and because this augments physiologic release rather
than broadly increasing circulating monoamines, it can lessen
abrupt orthostatic vasodilatory effects compared with MAO-A
inhibition.
Incorrect (A) — MAO-A inhibition raises peripheral and central
monoamines and can worsen orthostatic hypotension through
enhanced peripheral catecholamines and pharmacodynamic
interactions with α-1 blockade.
Incorrect (B) — Reuptake blockade increases synaptic
,monoamines but may lead to higher peripheral monoamine
levels and can exacerbate orthostatic symptoms; NET inhibition
particularly raises peripheral noradrenaline.
Incorrect (C) — VMAT inhibition reduces vesicular storage and
impairs monoamine release, worsening mood and causing
autonomic instability; it is not an antidepressant strategy per
Stahl.
Teaching point
Presynaptic α-2 blockade increases physiological transmitter
release with potentially lower peripheral orthostatic impact.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2
Reference
Ch. 1 — Chemical Neurotransmission — Transporters and
reuptake selectivity
Stem
A 28-year-old patient with anxious depression needs a
medication targeting both presynaptic SERT and NET but with
preferential blockade of SERT. Based on transporter
pharmacology in Ch. 1, which property of a reuptake inhibitor
would most reliably produce greater serotonergic than
noradrenergic reuptake inhibition at therapeutic doses?
, A. Higher affinity (lower Ki) for SERT than NET.
B. Longer half-life to permit accumulation at synapses.
C. Strong inhibition of VMAT to reduce noradrenaline storage.
D. Partial agonism at postsynaptic 5-HT1A receptors.
Correct answer
A
Rationales
Correct (A) — Reuptake selectivity depends on relative affinity
for transporters; a compound with substantially higher affinity
for SERT than NET will preferentially block serotonin reuptake at
therapeutic concentrations. Stahl emphasizes affinity and
selectivity as determinants of clinical pharmacology of
transporter inhibitors.
Incorrect (B) — Half-life affects dosing and accumulation but
not intrinsic selectivity between transporters.
Incorrect (C) — VMAT inhibition reduces vesicular monoamine
storage and decreases release, which does not create selective
reuptake blockade.
Incorrect (D) — 5-HT1A partial agonism modifies
postsynaptic/autoreceptor signaling but does not confer
transporter selectivity.
Teaching point
Transporter selectivity is determined primarily by drug affinity
(Ki) for each transporter, not half-life.
NEUROSCIENTIFIC BASIS AND PRACTICAL
APPLICATIONS
5TH EDITION
AUTHOR(S)STEPHEN M. STAHL
TEST BANK
1
Reference
Ch. 1 — Chemical Neurotransmission — Monoamine synthesis,
vesicular storage, and release
Stem
A 62-year-old patient with late-onset depressive symptoms and
orthostatic hypotension is being considered for an
antidepressant. The patient’s chart notes prior sensitivity to
drugs that increase synaptic monoamines and long-standing
hypertension controlled on an α-1 blocker. Which
pharmacologic approach best minimizes further orthostatic risk
while increasing synaptic monoamine tone through presynaptic
mechanisms?
,A. Inhibit monoamine oxidase A (MAO-A) to reduce monoamine
breakdown.
B. Block reuptake transporters (NET and SERT) to increase
synaptic monoamines.
C. Inhibit vesicular monoamine transporter (VMAT) to reduce
vesicular storage.
D. Use a drug that antagonizes presynaptic α-2 autoreceptors to
enhance release.
Correct answer
D
Rationales
Correct (D) — Antagonizing presynaptic α-2 autoreceptors
disinhibits transmitter release, increasing synaptic monoamines
(noradrenaline/serotonin) via enhanced exocytosis without
directly blocking peripheral α-1 receptors or causing
accumulation from inhibited breakdown. Stahl explains
presynaptic autoreceptor blockade as a mechanism to increase
release, and because this augments physiologic release rather
than broadly increasing circulating monoamines, it can lessen
abrupt orthostatic vasodilatory effects compared with MAO-A
inhibition.
Incorrect (A) — MAO-A inhibition raises peripheral and central
monoamines and can worsen orthostatic hypotension through
enhanced peripheral catecholamines and pharmacodynamic
interactions with α-1 blockade.
Incorrect (B) — Reuptake blockade increases synaptic
,monoamines but may lead to higher peripheral monoamine
levels and can exacerbate orthostatic symptoms; NET inhibition
particularly raises peripheral noradrenaline.
Incorrect (C) — VMAT inhibition reduces vesicular storage and
impairs monoamine release, worsening mood and causing
autonomic instability; it is not an antidepressant strategy per
Stahl.
Teaching point
Presynaptic α-2 blockade increases physiological transmitter
release with potentially lower peripheral orthostatic impact.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2
Reference
Ch. 1 — Chemical Neurotransmission — Transporters and
reuptake selectivity
Stem
A 28-year-old patient with anxious depression needs a
medication targeting both presynaptic SERT and NET but with
preferential blockade of SERT. Based on transporter
pharmacology in Ch. 1, which property of a reuptake inhibitor
would most reliably produce greater serotonergic than
noradrenergic reuptake inhibition at therapeutic doses?
, A. Higher affinity (lower Ki) for SERT than NET.
B. Longer half-life to permit accumulation at synapses.
C. Strong inhibition of VMAT to reduce noradrenaline storage.
D. Partial agonism at postsynaptic 5-HT1A receptors.
Correct answer
A
Rationales
Correct (A) — Reuptake selectivity depends on relative affinity
for transporters; a compound with substantially higher affinity
for SERT than NET will preferentially block serotonin reuptake at
therapeutic concentrations. Stahl emphasizes affinity and
selectivity as determinants of clinical pharmacology of
transporter inhibitors.
Incorrect (B) — Half-life affects dosing and accumulation but
not intrinsic selectivity between transporters.
Incorrect (C) — VMAT inhibition reduces vesicular monoamine
storage and decreases release, which does not create selective
reuptake blockade.
Incorrect (D) — 5-HT1A partial agonism modifies
postsynaptic/autoreceptor signaling but does not confer
transporter selectivity.
Teaching point
Transporter selectivity is determined primarily by drug affinity
(Ki) for each transporter, not half-life.
