CNS Drugs in the Top 300 Prescription Drugs

Since excitatory and inhibitory neurotransmitters are implicated in several pathological processes affecting the CNS, altering neurotransmitter kinetics and dynamics provides a mechanism for pharmacological intervention. CNS drugs in the Top 300 dispensed in 2017 include receptor modulators, direct receptor agonists or antagonists, inhibitors of neurotransmitter degradation, and inhibitors of neurotransmitter reuptake (Tables 2‑7).2

Table 2. Drugs in the Top 300 Affecting GABAergic and Glutamatergic Neurotransmission.2
Mechanisms of action* Drugs* Indications*
Benzodiazepine GABAA‑receptor modulators Lorazepam
Diazepam
Temazepam
Clonazepam
Anxiety disorders
Seizures disorders
Insomnia
Alcohol withdrawal
Sedation
Muscle spasm
Non-benzodiazepine GABAA‑receptor modulator Eszopiclone Insomnia
Non-benzodiazepine GABAB‑receptor agonism Baclofen Spasticity associated with spinal cord injury and motor neuron diseases (e.g., multiple sclerosis)
Non-benzodiazepine GABAB‑receptor modulator Zolpidem Hypnosis
Glutamatergic NMDA‑receptor antagonism Memantine Alzheimer’s disease
*FDA-approved information on specific agents is available at DailyMed - the website is a user-friendly, look-up-and-download resource that provides comprehensive, up-to-date information on individual drugs.3
Table 3. Drugs in the Top 300 Affecting Dopaminergic and Central Cholinergic Neurotransmission.2
Mechanisms of action* Drugs* Indications*
Dopamine precursor

Provides substrate for increased dopamine synthesis
Levodopa Parkinson’s disease
Dopamine D3‑receptor agonism Pramipexole
Ropinirole
Parkinson’s disease
Partial agonism at D2 and 5‑HT1A receptors;
Antagonism at 5‑HT2A receptors
Aripiprazole Schizophrenia
Major depressive disorder
Autism-associated irritability
Dopamine D2‑receptor antagonism Haloperidol Schizophrenia
Atypical antipsychotic agents

Dopamine D2‑ and serotonin 5‑HT2‑receptor antagonism
Risperidone
Olanzapine
Ziprasidone
Quetiapine
Lurasidone
Schizophrenia
Depression
Bipolar disorder
Autism (risperidone)
Muscarinic receptor antagonism

Reduces cholinergic tone by modifying the actions of striatal cholinergic interneurons
Benztropine Parkinson’s disease
Extrapyramidal disease
Inhibitor of acetylcholine degradation

Inhibits acetylcholinesterase by binding to its active site
Donepezil Alzheimer’s disease
*FDA-approved information on specific agents is available at DailyMed - the website is a user-friendly, look-up-and-download resource that provides comprehensive, up-to-date information on individual drugs.3
Table 4. Drugs in the Top 300 Affecting Serotonergic and Central Adrenergic Neurotransmission.2
Mechanisms of action* Drugs* Indications*
Storage inhibitors Displace 5‑HT, NE, and DA from storage vesicles in presynaptic nerve terminals Amphetamine
Methylphenidate
Lisdexamfetamine dimesylate
Dexmethylphenidate hydrochloride
Amphetamine aspartate; amphetamine sulfate; dextroamphetamine saccharate; dextroamphetamine sulfate
Attention-deficit hyperactivity disorder (ADHD)
Narcolepsy
Binge eating disorder
Tricyclic antidepressant Inhibits the uptake of 5‑HT and NE from the synaptic cleft by blocking 5‑HT and NE transporters enhancing postsynaptic responses Amitriptyline Depression
Selective serotonin reuptake inhibitors (SSRI) Selectively inhibit the reuptake of 5‑HT from the synaptic cleft by blocking 5‑HT transporters enhancing postsynaptic responses Citalopram
Escitalopram
Fluoxetine
Sertraline
Paroxetine
Vilazodone
Depression
Obsessive-compulsive disorder
Anxiety disorders
Serotonin-norepinephrine reuptake inhibitors (SNRI) Inhibit the reuptake of 5‑HT and NE from the synaptic cleft by blocking 5‑HT and NE transporters enhancing postsynaptic responses Venlafaxine
Duloxetine
Desvenlafaxine
Milnacipran
Major depressive disorder
Anxiety disorders
Fibromyalgia (milnacipran)
Norepinephrine reuptake inhibitors (NRI) Inhibit the reuptake of NE from the synaptic cleft by blocking NE transporters enhancing postsynaptic responses Doxepin Depression
Anxiety disorders
Atypical antidepressant Weak inhibitor of 5‑HT and NE uptake Bupropion Depression
Blocks 5‑HT2A and 5‑HT2C receptors and α2‑adrenergic autoreceptors decreasing 5‑HT and increasing NE neurotransmission Mirtazapine Depression
Postsynaptic 5‑HT receptor antagonism Trazodone Depression
Anxiety disorders
Insomnia
Serotonin receptor agonism Selective 5‑HT-receptor agonism Buspirone Anxiety disorders
Partial agonism at 5‑HT1 receptors and inhibition of 5‑HT transporters Vilazodone Depression
Causes vasoconstriction mediated by 5‑HT1 receptors expressed in the cerebral vasculature Sumatriptan Migraine headache
Serotonin receptor antagonism Blocks 5‑HT receptors with variable selectivity Ondansetron Nausea
PIP2-dependent signaling blockade Inhibits central adrenergic, muscarinic, and serotonergic neurotransmission Lithium Bipolar disorder
*FDA-approved information on specific agents is available at DailyMed - the website is a user-friendly, look-up-and-download resource that provides comprehensive, up-to-date information on individual drugs.3
Table 5. Drugs that Affect Electrical Neurotransmission in the CNS.2
Mechanisms of action* Drugs* Indications*
Sodium channel inhibitors Inactivate voltage-gated sodium channels in cortical neurons and reduces action potential generation. Phenytoin Tonic-clonic seizures
Focal seizures
Status epilepticus
Carbamazepine Tonic-clonic seizures
Focal seizures
Bipolar disorder
Trigeminal neuralgia
Oxcarbazepine Focal seizures
Lamotrigine Tonic-clonic seizures
Focal seizures
Atypical absence seizures
Bipolar disorders
Calcium channel inhibitors Inhibit high-voltage-activated (HVA) calcium channels Pregabalin Focal seizures
Postherpetic neuralgia
Gabapentin Focal seizures
Peripheral diabetic neuropathy
Fibromyalgia
Postherpetic neuralgia
Neuropathic pain (spinal injury)
Inhibits low-threshold T-type calcium channels Divalproex Complex partial seizures
Complex absence seizures
Manic episodes associated with bipolar disorders

Migraine (prophylaxis)

Benzodiazepine GABAA-receptor modulators Potentiate GABA-mediated inhibition to increase chloride conductance Clonazepam
Diazepam
Lorazepam
Status epilepticus
Tonic-clonic seizures
Focal seizures
Absence seizures
Skeletal muscle spasm
Other antiepileptic drugs Mechanisms unknown Topiramate Tonic-clonic seizures
Focal seizures
Migraine (prophylaxis)
Levetiracetam Tonic-clinic seizures
Focal seizures
Myoclonic seizures
*FDA-approved information on specific agents is available at DailyMed - the website is a user-friendly, look-up-and-download resource that provides comprehensive, up-to-date information on individual drugs.3
Table 6. Other Centrally Acting Muscle Eelaxants.2
Mechanisms of action* Drugs* Indications*
Reduction of tonic somatic motor activity, influencing both gamma (γ) and alpha (α) motor systems Cyclobenzaprine hydrochloride Skeletal muscle spasm of local origin
Central alpha2‑adrenergic receptor agonism Tizadine Spasticity
Alters interneuronal activity in in the descending reticular formation and the spinal cord Carisopradol Acute, painful musculoskeletal conditions in adults
Produces CNS depression by an unknown mechanism Metaxalone Acute, painful musculoskeletal conditions in adults
Non-benzodiazepine GABAB‑receptor agonism Baclofen Spasticity associated with motor neuron diseases (e.g., multiple sclerosis) and spinal cord injury
*FDA-approved information on specific agents is available at DailyMed - the website is a user-friendly, look-up-and-download resource that provides comprehensive, up-to-date information on individual drugs.3
Table 7. Anorectics.2
Mechanisms of action* Drugs* Indications*
Displaces 5-HT, DA, and NE from storage vesicles in presynaptic nerve terminals Phentermine To suppresses appetite as short-term (a few weeks) adjunct in a regimen of weight reduction based on exercise, behavioral modification and caloric restriction in the management of exogenous obesity in the presence of other risk factors (e.g., controlled hypertension, diabetes, and hyperlipidemia).
Male and female hormone modulator Cyanocobalamin To temporarily decrease appetite and increase energy while maintaining a low calorie diet for weight reduction
*FDA-approved information on specific agents is available at DailyMed - the website is a user-friendly, look-up-and-download resource that provides comprehensive, up-to-date information on individual drugs.3