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Pharmacology of Anxiolytic/
Sedative-Hypnotics
Philip G. Janicak, MD
Professor of Psychiatry and Pharmacology
University of Illinois at Chicago

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Abstract
Recent anxiolytic and sedative-hypnotic agents offer
comparable efficacy, fewer serious adverse effects, and less risk of
a fatal consequence due to accidental or intentional overdose in
comparison to alcohol, barbiturates and other non-barbiturate
agents (e.g., meprobamate). Unfortunately, they have not entirely
eliminated the hazards of tolerance, dependency, and withdrawal
syndromes, although they have a lower abuse potential than their
predecessors.
For these reasons, it is important to become
knowledgeable about the basic pharmacology of these drugs, in
addition to their appropriate clinical indications, dosages, and
duration of usage. Most importantly, their limitations must receive
as much attention as their assets.
pharmacology of anxiolytic/sedative-hypnotics

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pharmacology of anxiolytic/sedative-hypnotics
Objectives
Review diagnostic indications for anxiolytic/
sedative-hypnotics
Review different classes of antianxiety and
sedative-hypnotic agents in terms of their
pharmacodynamics; pharmacokinetics;
adverse effects; and potential for drug
interactions.
Review treatment strategies for anxiety and
sleep disorders.

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pharmacology of anxiolytic/sedative-hypnotics
Anxiety
Natural human experience
Subjective qualities of fear or related emotions
Ensures survival and adaptation
In excess, can cripple and destroy

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pharmacology of anxiolytic/sedative-hypnotics
Anxiety Symptoms
Anxiety symptoms are associated
with numerous medical conditions:
Cardiovascular disease
Endocrine disease
Gastrointestinal disease
Neurologic disease
Drug-induced

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pharmacology of anxiolytic/sedative-hypnotics
Indications for Antianxiety/Sedative-Hypnotics
Generalized anxiety disorder (GAD)
Phobic disorders
Psychological factors affecting medical condition
Panic disorder
Obsessive-compulsive disorder
Posttraumatic stress disorder
Sleep disorders (dyssomnias; parasomnias)

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pharmacology of anxiolytic/sedative-hypnotics
GAD
Represents up to 50% of anxious
patients seen by physicians
Increased annual medical expenses
Often unnecessary medical consultations
55 million prescriptions for BZDs in 1989
Anxiolytic agents fourth most prescribed
class of medication

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Phobic Disorders
Disabling anxiety (at times associated
with panic attacks) and avoidance
Agoraphobia
Social phobia (Social Anxiety Disorder)
Specific phobia
pharmacology of anxiolytic/sedative-hypnotics

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Psychological Factors
Affecting Medical Condition
Psychologically meaningful environmental stimuli
Temporally related to the initiation or exacerbation
of a physical condition
Demonstrable organic pathology (e.g., rheumatoid
arthritis)
Known physiological process (e.g., migraine)
pharmacology of anxiolytic/sedative-hypnotics

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pharmacology of anxiolytic/sedative-hypnotics
Panic Disorder
Sudden, spontaneous, unexpected feelings of
terror and anxiety
The autonomic equivalence of anxiety
The desire to flee the situation and return to
a safe place
A phobic avoidance of the places where
such attacks occur

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Symptomatology of Panic Attacks
Shortness of breath
/smothering sensations
Dizziness, unsteady
feelings, or faintness
Palpitations/tachycardia
Trembling/shaking
Sweating
Choking
Nausea/abdominal distress
Depresonalization/
derealization
Paresthesias
Flushes/chills
Chest pain or discomfort
Fear of dying
Fear of going crazy or doing
something uncontrolled
pharmacology of anxiolytic/sedative-hypnotics

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Course of Illness
Panic
GAD
Normal
anxiety level
time
pharmacology of anxiolytic/sedative-hypnotics

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pharmacology of anxiolytic/sedative-hypnotics
Obsessive-Compulsive Disorder (OCD)
Recurrent obsessions and/or compulsions:
Cause marked distress, are time-consuming, or
interfere with functioning
Are recognized as excessive or unreasonable
Are not due to the effect of a substance or general
medical condition

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pharmacology of anxiolytic/sedative-hypnotics
Obsessions in OCD
Contamination
Pathological doubt
Aggressive impulses
Somatic concerns
Need for symmetry
Sexual impulses

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pharmacology of anxiolytic/sedative-hypnotics
Compulsive Behaviors in OCD
Cleaning
Washing
Checking
Excessive ordering/arranging
Counting
Repeating
Collecting

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Posttraumatic Stress Disorder (PTSD)
Due to an unusual experience that would be very stressful for
almost anyone (e.g., combat, rape, sudden unexpected
death of a loved one)
Symptoms include:
Intrusive recollections; frightening dreams; sense of event recurring
Intensive physiological stress; hyperarousal
Emotional numbing
Persistent avoidance of stimuli associated with the trauma
High comorbidity with other psychiatric disorders
Increase suicide attempt risk
Female-to-male lifetime prevalence ratio of 2:1
pharmacology of anxiolytic/sedative-hypnotics

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Sleep Disorders
Dyssomnias (difficulty initiating or maintaining sleep
or not feeling rested)
Primary Insomnia
Primary Hypersomnia
Circadian Rhythm Disorder
Parasomnias (abnormal event)
Nightmare Disorder
Sleep Terror Disorder
Sleepwalking Disorder
pharmacology of anxiolytic/sedative-hypnotics

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pharmacology of anxiolytic/sedative-hypnotics
Pharmacodynamics
Benzodiazepines
Specific binding site associated with GABAA receptor-
chloride ion channel
Potentiate GABA
Serotonergic effects (e.g., clonazepam)
Azapirone (e.g., buspirone)
5-HT1A agonist: acutely, ↓ firing, in dorsal raphe nuclei;
chronically, receptor desensitization → ↓ activity
Beta-blockers
β receptors central and peripheral, post synaptic
Clonidine
Agonist at α2 receptors, central, pre-synaptic
Antidepressants

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pharmacology of anxiolytic/sedative-hypnotics
GABA Function and Distribution
Inhibitory neurotransmitter
Widely distributed throughout CNS
Local inhibitory action, therefore
rapidly alters neuronal output
Desensitization to inhibitory effects
with chronic stimulation of GABA

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GABAA-BZD Supramolecular Complex

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S.M. Paul, 1995
GABAA Receptor Structure
Benzodiazepines
Agonists
Antagonists-
Inverse Agonists
DBI Peptides
Convulsants
Picrotoxin
TBPS
Cl-
GABA Agonists
Muscimol
GABA Antagonists
Bicuculline
Barbiturates
Neuroactive Steroids
Alcohols
Anesthetics

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GABAA receptorCytoplasm
Benzodiazepine-
binding domain
pharmacology of anxiolytic/sedative-hypnotics

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BZD Receptors
Type I
Predominates in cerebellum
Anxiolytic properties
Less sedative properties
Type II
Located in cortex, hippocampus, spinal cord
No anxiolytic properties
Sedative properties
Type III
Located in peripheral tissue
No anxiolytic properties
? other properties
pharmacology of anxiolytic/sedative-hypnotics

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BZD Receptor Activity
Full Agonist
Partial
Agonist Antagonist
Partial Inverse
Agonist
Full Inverse
Agonist
Anxiolytic
Sed-Hypnotic
Myorelaxant
Anticonvulsant
Amnestic
Dependency
Anxiolytic No clinical
effect
Promnestic
Anxiogenic
Pro-convulsant
Promnestic
Anxiolytic
Convulsant
pharmacology of anxiolytic/sedative-hypnotics

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Non-Benzodiazepine Agents
Imidazopyridines (e.g., zolpidem, alpidem)
Pyrazolopyrimidine (e.g., zaleplon)
Cyclopyrralone (e.g., zopiclone)
Sedating antidepressants (e.g., trazodone)
pharmacology of anxiolytic/sedative-hypnotics

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Non-Benzodiazepine Agents (con’t)
Antihistamines (e.g., diphenhydramine)
Natural Remedies (e.g., melatonin, valerian)
B-carbolines (e.g., abecarnil)
BZD structural derivatives (e.g., biretazanil)
pharmacology of anxiolytic/sedative-hypnotics

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pharmacology of anxiolytic/sedative-hypnotics
Serotonin Model
Majority of 5-HT pathways originate
in the dorsal raphe (DR)
DR innervates cortex, hypothalamus,
thalamus, and limbic system
5-HT mediates behavioral effects in
animal models and humans

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Serotonin Receptors
5-HT1A -Anxiety, alcoholism, sexual function
5-HT1C -Anxiety, migraine pain
5-HT1D -Migraine pain
5-HT2 -Anxiety, depression, schizophrenia
negative symptoms, sexual function
5-HT3 -Migraine pain, emesis, schizophrenia
(e.g., ondansetron)
5-HT4 -Anxiety, schizophrenia?
pharmacology of anxiolytic/sedative-hypnotics

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Serotonin Agents: Indications for
Anxiety-Related Disorders
SSRI
Sertraline -OCD; PD; PTSD
Paroxetine -OCD; PD; SAD; GAD
Fluoxetine -OCD; BN; PMDD
Fluvoxamine-OCD
Venlafaxine -GAD
Buspirone -GAD
pharmacology of anxiolytic/sedative-hypnotics

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Noradrenergic Model
Hypersensitivity to autonomic nervous system
Locus coeruleus (LC)
Stimuli → norepinephrine release → stimulation
of the sympathetic nervous system
pharmacology of anxiolytic/sedative-hypnotics

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Norepinephrine Receptors
Locus coeruleus
Alpha -2 adrenergic receptors
somatodendritic autoreceptors
terminal autoreceptors
negative feedback system
antagonists are anxiogenic
agonists may be anxiolytic and decrease withdrawal
symptoms (e.g., clonidine)
Beta adrenergic receptors
Beta-blockers (e.g., propranolol)
Social phobia
Performance anxiety
pharmacology of anxiolytic/sedative-hypnotics

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Pharmacokinetics: Benzodiazepines
Absorption: rapid absorption, except clorazepate
Onset of action: increase lipid solubility → faster onset
Duration of action: single dose with increased lipid solubility
→ faster redistribution to fat tissues→
shorter duration of action. Chronic use:
in equilibrium with fat tissues
Half life: In part, determines duration of action
Metabolism: lorazepam, oxazepam, temazepam not
metabolized by liver
pharmacology of anxiolytic/sedative-hypnotics

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Drug Interactions: Benzodiazepines
Additive pharmacodynamic effects (e.g., alcohol)
BZD withdrawal when other drugs that increase
seizure risk are also taken
Inhibit BZD metabolism (e.g., nefazodone via
P450 3A 3/4 inhibits metabolism of triazolam)
Diazepam may increase levels of digoxin and
phenytoin
pharmacology of anxiolytic/sedative-hypnotics

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Adverse Effects: Benzodiazepines
Sedation and impairment of performance
Psychomotor skills: driving; engaging in dangerous physical
activities; using hazardous machinery, especially during
initial phase of treatment
Memory impairment
Anterograde amnesia (desired before surgery, other
procedures).
Dose-related, and tolerance may not develop.
Most likely with triazolam
Disinhibition
Possible risk factors: history of aggression, impulsivity,
borderline or antisocial personality
pharmacology of anxiolytic/sedative-hypnotics

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Abuse, Dependence, Withdrawal, and
Rebound Anxiety: Benzodiazepines
Abuse potential decreased when properly prescribed and supervised.
Dependence may occur at usual doses taken beyond several weeks.
Withdrawal may occur even when discontinuation is not abrupt (e.g.,
by 10% every 3 days). Symptoms include: tachycardia, increased blood
pressure, muscle cramps, anxiety, insomnia, panic attacks, impairment
of memory and concentration, perceptual disturbances, derealization,
hallucinations, hyperpyrexia, seizures. May continue for months.
Rebound anxiety: return of target symptoms, with increase intensity.
pharmacology of anxiolytic/sedative-hypnotics

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Pharmacokinetics/Pharmacodynamics:
Buspirone
Onset of action (i.e., weeks versus days)
No sedation or impairment of performance
No cross-tolerance with BZDs
No tolerance or withdrawal
No abuse potential
pharmacology of anxiolytic/sedative-hypnotics

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Adverse Effects: Buspirone
Nausea
Headache
Insomnia, nervousness
Restlessness
Dizziness, lightheadedness
pharmacology of anxiolytic/sedative-hypnotics

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CLINICAL PRESENTATION TREATMENT STRATEGY
PSYCHOTHERAPY:
Supportive, Cognitive-Behavioral
or Insight-Oriented
Acute anxiety (mild)
Acute anxiety (more severe) (start) Benzodiazepine (BZD)
plus Psychotherapy
(may start)
(insufficient response)
Treatment Strategy for GAD
(may add)
(insufficient response)
(may try)

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CLINICAL PRESENTATION TREATMENT STRATEGY
Buspirone (up to 90 mg/day for
up to 6 weeks) plus CBT
Chronic anxiety
(no prior BZD therapy)
Venlafaxine
(may start)
(insufficient response)
Treatment Strategy for GAD
(insufficient response)

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CLINICAL PRESENTATION TREATMENT STRATEGY
Buspirone or Venlafaxine plus
BZD initially, then taper BZD
plus CBT
Chronic anxiety,
prior BZD therapy
Chronic anxiety with panic
or depressive symptoms
(may start)
Buspirone or Venlafaxine
plus BZD for longer period
plus CBT
(may start)
(insufficient response)
Treatment Strategy for GAD
Other Antidepressants (TCA,
SSRI, MAOI) w/wo a BZD or
Buspirone
(insufficient response)

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CLINICAL PRESENTATION TREATMENT STRATEGY
Cognitive Behavioral TherapySocial Phobia, Generalized
(Social Anxiety Disorder)
(may start)
(insufficient response)
Treatment Strategy
for PHOBIC Disorders
(or)
Selective Serotonin Reuptake
Inhibitor (e.g., Paroxetine)
(insufficient response)

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CLINICAL PRESENTATION TREATMENT STRATEGY
BEHAVIORAL THERAPY
PLUS SSRI
MAOI (must wait at least 2 weeks
after discontinuation of SSRI [longer
for fluoxetine] before starting MAOI)
(insufficient response)
Treatment Strategy
for PHOBIC Disorders
or
Alprazolam
or
Clonidine

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CLINICAL PRESENTATION TREATMENT STRATEGY
Cognitive Behavioral Therapy
Systematic desensitization
Specific Phobia
B-blocker (e.g., performance anxiety)
(start)
(insufficient response)
Treatment Strategy
for PHOBIC Disorders
MAOI (e.g., phenelzine)
(insufficient response)

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CLINICAL PRESENTATION TREATMENT STRATEGY
Behavioral Therapy only
(may require several months)
Cognitive
In-vivo exposure
Relaxation
Systematic desensitization
Panic attacks (mild)
w/wo agoraphobia
(start)
(insufficient response)
Treatment Strategy for PANIC Disorder with
or without Agoraphobia
(may add)
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.

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CLINICAL PRESENTATION TREATMENT STRATEGY
SSRI plus Behavioral TherapyPanic attacks (moderate)
w/wo agoraphobia
(may start)
(insufficient response)
(or)
Other Antidepressant (e.g.,
Venlafaxine, TCA) plus
Behavioral Therapy
(insufficient response)
Treatment Strategy for PANIC Disorder with
or without Agoraphobia
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.

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CLINICAL PRESENTATION TREATMENT STRATEGY
ALPRAZOLAM/CLONAZEPAM
plus Behavioral Therapy
(insufficient response)
Treatment Strategy for PANIC Disorder with
or without Agoraphobia
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.

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CLINICAL PRESENTATION TREATMENT STRATEGY
TCA/SSRI and Behavioral TherapyPanic attacks (severe)
w/wo agoraphobia
Alprazolam/Clonazepam
for first month
(start)
(plus)
(insufficient response)
Treatment Strategy for PANIC Disorder with
or without Agoraphobia
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.

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Alprazolam/Clonazepam
indefinitely
CLINICAL PRESENTATION TREATMENT STRATEGY
TCA/SSRI and Behavioral Therapy
Treatment Strategy for PANIC Disorder with
or without Agoraphobia
(plus)
(insufficient response)
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.

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CLINICAL PRESENTATION TREATMENT STRATEGY
MONOAMINE OXIDASE INHIBITOR
(N.B. SSRI) must be stopped prior to
beginning MAOI:
Fluoxetine, at least 5 weeks
Other SSRIs, at least 2 weeks
Valproate w/wo BZD
(insufficient response)
(may try)
Treatment Strategy for PANIC Disorder with
or without Agoraphobia
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.

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CLINICAL PRESENTATION TREATMENT STRATEGY
Behavioral Therapy
(e.g., exposure and response
prevention)
Mild symptoms (may start)
(insufficient response)
Treatment Strategy for OBSESSIVE-
COMPULSIVE and Related Disorders
(may add)
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.

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CLINICAL PRESENTATION TREATMENT STRATEGY
SSRI
Fluvoxamine
Sertraline
Paroxetine
Citalopram
Fluoxetine
Moderate to severe
symptoms
(start)
(insufficient response)
Clomipramine
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.
Behavioral Therapy
(plus)
(or)
Treatment Strategy for OBSESSIVE-
COMPULSIVE and Related Disorders

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CLINICAL PRESENTATION TREATMENT STRATEGY
Alternate SRI
(insufficient response)
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.
Treatment Strategy for OBSESSIVE-
COMPULSIVE and Related Disorders
(insufficient response)
Clonazepam/Buspirone
plus SRI

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CLINICAL PRESENTATION TREATMENT STRATEGY
Pimozide/Haloperidol/Risperidone
or Lithium w/wo SRI
Trichotillomania
Tics (e.g., Tourette’s)
Delusional symptoms
MAOI (SRI must be completely
cleared first)
(may start)
(insufficient response)
(insufficient response)
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.
Treatment Strategy for OBSESSIVE-
COMPULSIVE and Related Disorders
(may consider)

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CLINICAL PRESENTATION TREATMENT STRATEGY
Somatic Therapy
ECT
Neurosurgery
TMS (?)
Severe, unremitting
course (e.g., 5 years;
failed trials with SSRI,
CMI, MAOI; severe
dysfunction)
(consider)
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.
Treatment Strategy for OBSESSIVE-
COMPULSIVE and Related Disorders

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CLINICAL PRESENTATION TREATMENT STRATEGY
Clarify diagnosis
treat any medical or psychiatric disorder
check for non-prescribed drugs
Transient or short-
term insomnia
(first)
(insufficient response or no
other disorder discovered)
Treatment Strategy for SLEEP Disorders
Adapted from Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.

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CLINICAL PRESENTATION TREATMENT STRATEGY
Nonpharmacological therapies
Stimulus control
Sleep restriction
Relaxation techniques
Paradoxical intention
Sleep hygiene techniques
Treatment Strategy for SLEEP Disorders
(insufficient response)
Adapted from Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.

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CLINICAL PRESENTATION TREATMENT STRATEGY
Short- to intermediate-acting
BZD Sedative-Hypnotic (e.g.,
estazolam 0.5-1 mg QHS)
(insufficient response)
Zolpidem or Zaleplon
(5-20 mg QHS)
(or)
Treatment Strategy for SLEEP Disorders
Adapted from Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.

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CLINICAL PRESENTATION TREATMENT STRATEGY
Non-pharmacological therapies
w/wo sedating antidepressant
Chronic insomnia
(≥7-12 weeks)
(start)
e.g., trazodone (25-50 mg QHS)
Treatment Strategy for SLEEP Disorders
COMBINED TREATMENT
non-pharmacological and
intermittent, sedative-
hypnotic when necessary
(insufficient response)
Adapted from Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.

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Generic Names Trade Names Daily Dosage
(mg/day)
BENZODIAZEPINES
Chlordiazepoxide Librium, others 10-100
Diazepam Valium, others 2-40
Oxazepam Serax, others 30-120
Chlorazepate Tranxene, others 15-60
Lorazepam Ativan 1-10
Prazepam Centrax 20-60
Halazepam Paxipam 60-160
Alprazolam Xanax 0.75-4
AZAPIRONES
Buspirone Buspar 15-60
ANTIDEPRESSANTS
SSRI Sertraline, others 25-250
Venlafaxine Effexor 75-375
ANTIANXIETY AGENTS

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Generic Names Trade Names Daily Dosage (mg /day)
BENZODIAZEPINES
Long-acting
Flurazepam Dalmane 15-45
Quazepam Doral 7.5-15
Intermediate-acting
Estazolam Prosom 0.5-2
Temazepam Restoril 15-45
Short-acting
Triazolam Halcion 0.125-0.25
NONBENZODIAZEPINE
Zolpidem Ambien 5-20
Zaleplon Sonata 5-20
SEDATING ANTIDEPRESSANTS
Trazodone Dyserel 25-100
BARBITURATE-LIKE
Chloral Hydrate Notec 500-1500
OTHER
Melatonin 0.3-2
SEDATIVE-HYPNOTICS

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References
Ayd FJ Jr, Janicak PG, Davis JM, Preskorn SH. Advances in the
pharmacotherapy of anxiety-related disorders. In: Janicak PG, ed.
Principles and Practice of Psychopharmacotherapy Update. Baltimore,
MD: Williams & Wilkins; 1996. Vol 1.
Janicak PG, Ayd FJ Jr. Sedatives and hypnotics in the elderly patient.
In: Nelson JC, ed. Geriatric Psychopharmacology. New York, NY:
Marcel-Dekker; 1998:347-366.
Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr. Principles and Practice
of Psychopharmacotherapy. 3rd Ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2001:463-558.
Israni TH, Janicak PG, Davis JM. Obsessive compulsive disorder. In:
Flaherty JA, Davis JM, Janicak PG, eds. Psychiatry: diagnosis and
therapy. 2nd ed. Norwalk, CN: Appleton & Lange; 1993:145-155.
pharmacology of anxiolytic/sedative-hypnotics