Molecular Neuropharmacology: A Foundation for Clinical Neuroscience

Citation

Nestler, E. J., Kenny, P. J., Russo, S. J., & Schaefer, A. (2020). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (4th ed.). McGraw Hill.

Chapter Summary

The book has twenty chapters in three parts: general principles of neuropharmacology and cell signalling, the major transmitter systems, and then the neuropharmacology of neural systems and disorders. The publisher describes it as covering general principles, nervous system function, drugs that act on neuronal and glial function, the major neurotransmitter systems in the brain and spinal cord, atypical neurotransmitters including peptides, growth factors and cytokines, and major brain and spinal cord systems at molecular, cellular and circuit levels in health and disease. The publisher markets the fourth edition as Nestler, Hyman, & Malenka's Molecular Neuropharmacology.

Part 1, Chapters 1–4: Fundamentals of Neuropharmacology

The four opening chapters are titled Basic Principles of Neuropharmacology (1), Cellular Basis of Communication (2), Synaptic Transmission (3) and Signal Transduction in the Brain (4). They move from the general logic of how drugs act on the nervous system through the electrical and synaptic basis of communication to intracellular signalling.

Part 2, Chapters 5–8: Neural Substrates of Drug Action

The chapters on transmitters are Excitatory and Inhibitory Amino Acids (5), Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin (6), Neuropeptides (7) and Atypical Neurotransmitters (8). Together they cover the classical fast transmitters, the diffusely projecting modulatory systems, and the peptide and non-classical signals that the publisher highlights as including growth factors and cytokines.

Part 3, Chapters 9–12: Body, Pain and Inflammation

The third part turns to systems and disorders. It begins with the Autonomic Nervous System (9), Neural and Neuroendocrine Control of the Internal Milieu (10), Pain (11) and Neuroinflammation (12).

Part 3, Chapters 13–16: Sleep, Cognition, Mood and Reinforcement

Sleep and Arousal (13), Higher Cognitive Function and Behavioral Control (14), Mood and Emotion (15) and Reinforcement and Addictive Disorders (16).

Part 3, Chapters 17–20: Psychotic, Degenerative and Vascular Disorders

Schizophrenia and Bipolar Disorder (17), Neurodegeneration (18), Seizure Disorders (19) and Stroke and Migraine (20).

Key Concepts

Chapters 1–4: Foundations

• Principles of neuropharmacology: the general rules for how drugs act on neural targets, set out before any single transmitter system.
• Synaptic transmission: the process by which neurons communicate across synapses.
• Signal transduction: the intracellular pathways through which receptor activation changes neuronal function.

Chapters 5–8: Transmitter Systems

• Amino acid transmitters: excitatory and inhibitory transmission in the brain and spinal cord.
• Widely projecting modulatory systems: monoamines, acetylcholine and orexin.
• Neuropeptides and atypical neurotransmitters: signals beyond the classical small-molecule transmitters.

Chapters 9–16: Systems and Behaviour

• Autonomic and neuroendocrine control: how the nervous system regulates the internal milieu.
• Pain and neuroinflammation: two chapters that link neural signalling to tissue and immune processes.
• Sleep, cognition, mood and reinforcement: behavioural domains with their own chapters, ending with addictive disorders.

Chapters 17–20: Disorders

• Psychotic and mood disorders: schizophrenia and bipolar disorder.
• Neurodegeneration, seizure disorders, stroke and migraine: neurological conditions treated mechanistically.

Critical Analysis

Strengths

• Mechanism first, then disease. Fundamental chapters on signalling and transmitters precede the disease chapters, so clinical conditions are discussed with the molecular background already in place. The publisher describes the aim as explaining the pathophysiology and neuropharmacology of the major neurologic and psychiatric disorders.
• Organisation by neural system and disorder. Part 3 gives each domain (pain, sleep, cognition, mood, reinforcement, psychosis, neurodegeneration, seizures, stroke and migraine) its own chapter, which makes the book easy to dip into by clinical topic.
• Broad view of signalling. The inclusion of neuropeptides, atypical neurotransmitters and neuroinflammation as chapters reflects the publisher's emphasis on signals beyond the classical transmitters, including growth factors and cytokines.
• Visual support. The publisher says tables, diagrams and figures illustrate neurochemistry and molecular neuroscience.

Limitations

• Demanding prerequisites. The book assumes cell and molecular biology and a prior course in neuroscience or neuroanatomy; it does not teach those from the start.
• Confined to the nervous system. Drugs acting on other body systems, and general pharmacokinetics for the whole pharmacopoeia, are outside its scope, so a general pharmacology text is still needed for a full pharmacology course.
• No dedicated chapters on some topics. The contents list has no chapters on neurodevelopmental disorders as such, or on anxiety as a separate topic (mood and emotion are combined in Chapter 15).
• Specialist depth. At twenty chapters on molecular detail, it is a graduate-level text, and parts will exceed the needs of a clinical course.

Where It Fits in the Course

The Biochemical Basis of Neuropharmacology (Cooper, Bloom and Roth, 2002) is a molecular introduction to neurotransmitters, receptors and synaptic signalling. Molecular Neuropharmacology covers comparable foundations in Parts 1 and 2 and then devotes the whole of Part 3 to systems and disorders, so it is the more recent choice when the goal is to understand current treatments and the diseases they target.

The other neuroscience books in this course list play different roles. Neuroscience: Exploring the Brain and Foundations of Neuroscience introduce the field to newcomers; Neuroanatomy and Neuroscience at a Glance and Neuroanatomy: Illustrated Colour Text give a visual map of structure and function; Purves' Neuroscience and From Neuron to Brain are comprehensive textbooks of cellular and systems neuroscience. Read Molecular Neuropharmacology after one of these, when you want to see how molecular mechanisms explain drug action and disease.

How to Use This Book

The book suits medical students, pharmacy and neuroscience graduates, psychiatry and neurology trainees and researchers who want a mechanistic account of drug action in the nervous system. Cell and molecular biology, basic pharmacology and an introductory neuroscience or neuroanatomy course are the sensible background.

A practical plan: read Part 1 first and in order, since the transmitter and disease chapters rely on its vocabulary of synaptic transmission and signal transduction. Then read the transmitter chapters (5 to 8) as the reference for the receptor and transmitter names used afterwards. In Part 3, choose chapters by topic: a psychiatry student might read 15 to 17 together, a neurology student 18 to 20, and a student interested in pain or inflammation 11 and 12. Use the tables and diagrams for revision, and pair the disorder chapters with a clinical text so the mechanisms are attached to presentation and treatment.