Barbiturates vs. Benzodiazepines

What's the Difference?

Barbiturates and benzodiazepines are both types of central nervous system depressants commonly used as sedatives, hypnotics, and anxiolytics. However, there are some key differences between the two. Barbiturates are older drugs that act as nonselective depressants, binding to multiple receptor sites in the brain. They have a higher risk of overdose and addiction potential, making them less commonly prescribed today. On the other hand, benzodiazepines are newer drugs that selectively bind to specific receptors, enhancing the effects of gamma-aminobutyric acid (GABA), a neurotransmitter that inhibits brain activity. Benzodiazepines have a lower risk of overdose and addiction compared to barbiturates, making them more widely used in clinical practice.


Chemical StructureDerived from barbituric acidDerived from diazepine ring
Mechanism of ActionEnhance GABA activityEnhance GABA activity
Therapeutic UsesSedation, anesthesia, anticonvulsantAnxiety, insomnia, muscle relaxation
Side EffectsRespiratory depression, dependence, addictionDrowsiness, dizziness, dependence
Duration of ActionShort to intermediateShort to long
Half-lifeVaries depending on the specific barbiturateVaries depending on the specific benzodiazepine
Drug InteractionsInteracts with many drugs, including alcoholInteracts with many drugs, including alcohol

Further Detail


Barbiturates and benzodiazepines are two classes of drugs commonly used for their sedative, hypnotic, and anxiolytic properties. While they share some similarities in their effects, mechanisms of action, and therapeutic uses, there are also significant differences between these two drug classes. This article aims to provide a comprehensive comparison of the attributes of barbiturates and benzodiazepines, shedding light on their pharmacology, side effects, potential for abuse, and clinical applications.


Barbiturates, such as phenobarbital and pentobarbital, act as central nervous system depressants by enhancing the inhibitory effects of the neurotransmitter gamma-aminobutyric acid (GABA) in the brain. They bind to specific GABA receptors, increasing the duration of GABA-mediated chloride channel opening, resulting in neuronal hyperpolarization and reduced excitability.

Benzodiazepines, including diazepam and alprazolam, also potentiate the effects of GABA but act on a different receptor subtype. They bind to the GABA-A receptor complex, increasing the frequency of chloride channel opening, leading to similar inhibitory effects on neuronal activity.

While both drug classes enhance GABAergic neurotransmission, barbiturates have a more direct effect on the GABA receptor, whereas benzodiazepines modulate the receptor's activity indirectly.

Therapeutic Uses

Barbiturates were historically used as sedatives, hypnotics, and anticonvulsants. However, due to their narrow therapeutic index and high potential for overdose, their clinical use has significantly declined. Today, they are primarily used in the treatment of certain seizure disorders, such as epilepsy, where other medications have proven ineffective.

Benzodiazepines, on the other hand, have a broader range of therapeutic applications. They are commonly prescribed for the short-term management of anxiety disorders, panic attacks, insomnia, muscle spasms, and alcohol withdrawal symptoms. Additionally, some benzodiazepines, like clonazepam, are effective anticonvulsants and are used in the treatment of epilepsy.

It is important to note that both drug classes should be used judiciously and for the shortest duration possible due to the risk of tolerance, dependence, and withdrawal symptoms upon discontinuation.

Side Effects

Barbiturates and benzodiazepines share several common side effects, including drowsiness, sedation, impaired coordination, and cognitive impairment. However, barbiturates tend to produce more pronounced sedation and respiratory depression compared to benzodiazepines.

Barbiturates are also associated with a higher risk of physical dependence and withdrawal symptoms upon discontinuation. Abrupt cessation of barbiturates can lead to potentially life-threatening withdrawal symptoms, including seizures and delirium. Benzodiazepines, while also capable of causing dependence, generally have a lower risk of severe withdrawal symptoms.

Another important distinction is the potential for overdose. Barbiturate overdose can be lethal, especially when combined with other central nervous system depressants, such as alcohol. Benzodiazepine overdose, although serious, is less likely to be fatal unless combined with other substances.

Abuse Potential

Both barbiturates and benzodiazepines have the potential for abuse and can produce a euphoric effect when taken in higher doses. However, barbiturates are considered to have a higher abuse potential compared to benzodiazepines.

Barbiturates were commonly abused in the past, leading to the development of physical and psychological dependence. Their abuse potential, combined with the risk of overdose, prompted stricter regulations and a decline in their clinical use.

Benzodiazepines, while still subject to abuse, are generally considered to have a lower risk of dependence and addiction. However, long-term use or misuse of benzodiazepines can lead to physical and psychological dependence, making it important to carefully monitor their use and gradually taper off the medication when discontinuing treatment.


In summary, barbiturates and benzodiazepines are two classes of drugs with similar therapeutic uses but distinct pharmacological properties, side effect profiles, and abuse potentials. Barbiturates directly enhance GABAergic neurotransmission, have a narrower therapeutic index, and are primarily used in the treatment of certain seizure disorders. Benzodiazepines indirectly modulate GABA receptors, have a broader range of clinical applications, and are commonly prescribed for anxiety, insomnia, and muscle spasms.

While both drug classes can cause sedation, impaired coordination, and cognitive impairment, barbiturates tend to produce more pronounced effects. Barbiturates also carry a higher risk of physical dependence, severe withdrawal symptoms, and overdose compared to benzodiazepines.

Ultimately, the choice between barbiturates and benzodiazepines depends on the specific clinical indication, patient characteristics, and the potential risks and benefits associated with each medication. It is crucial for healthcare professionals to carefully evaluate and monitor patients receiving these medications to ensure their safe and appropriate use.

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