CNS Pharmacology: Barbiturates, Antipsychotics, and Epilepsy

Posted on Jun 30, 2025 in Physical Education

Barbiturates: Potent CNS Depressants

Barbiturates are potent central nervous system (CNS) depressants. They are medicines that slow down brain or CNS activity. They can be very strong and risky if not used carefully. They are used to treat anxiety, sleep problems, and seizures. Common barbiturates include:

  1. Barbital
  2. Phenobarbital
  3. Mephobarbital
  4. Amobarbital
  5. Butabarbital
  6. Pentobarbital
  7. Secobarbital

Mechanism of Action of Barbiturates

  • Barbiturates work by increasing the effect of GABA, a calming brain chemical, which slows down brain activity, helping to induce sleep, reduce anxiety, and stop seizures.
  • They bind to an allosteric site (different from the benzodiazepine site).
  • At high concentrations, they can directly open chloride channels.

Structure-Activity Relationship (SAR) of Barbiturates

Barbiturates are derivatives of barbituric acid, having a cyclic structure with two nitrogen atoms and three carbonyl groups.

C5 Substitution

  • This is most critical for activity.
  • Dialkyl or aryl/alkyl substitution at C5 increases lipid solubility and CNS activity.
  • Aryl groups tend to prolong the action duration and enhance anticonvulsant activity.

N1 and N3 Substitution

  • Alkylation of nitrogen reduces polarity, increasing lipophilicity.
  • In general, substitution at N1 or N3 reduces anticonvulsant activity but may enhance hypnotic activity.

Unsaturation or Aromaticity

  • Introducing double bonds or an aromatic ring increases lipid solubility.

Antipsychotics: Managing Psychotic Disorders

Antipsychotics are drugs that have a specific sedative effect and improve the attitude and calm behavior of psychotic patients. They are also known as neuroleptics or major tranquilizers. They do not eliminate the disorder; they only decrease the symptoms.

Understanding Psychosis

Psychosis is a mental disorder characterized by a disconnection from reality.

Types of Psychotic Disorders

Psychosis can occur due to:

  • Schizophrenia
  • Bipolar disorder
  • Psychotic depression
  • Schizoaffective disorder
  • Drug-induced psychosis

Classification of Antipsychotics

  • Phenothiazines

    • Promazine hydrochloride
    • Chlorpromazine hydrochloride
    • Triflupromazine
    • Thioridazine hydrochloride
    • Perphenazine
    • Prochlorperazine maleate
    • Trifluoperazine

  • Ring Analogues of Phenothiazines

    • Chlorprothixene
    • Thiothexene
    • Loxapine succinate
    • Clozapine

  • Fluorobutyrophenones

    • Haloperidol
    • Droperidol
    • Risperidone

Phenothiazines: Mechanism and Uses

Phenothiazines are non-selective, competitive antagonists of D1 and D2 dopamine receptors, blocking dopamine activity at these receptor sites. These drugs are also known as tricyclic antipsychotics. They act on the CNS by causing moderate sedative and antiemetic effects. These include:

  1. Promazine hydrochloride
  2. Chlorpromazine hydrochloride
  3. Triflupromazine
  4. Thioridazine hydrochloride
  5. Perphenazine
  6. Prochlorperazine maleate
  7. Trifluoperazine

Mechanism of Action of Phenothiazines

Phenothiazines work by blocking dopamine (D1 & D2) receptors in the brain or CNS. This helps reduce symptoms like hallucinations, delusions, and agitation, making them effective in treating mental health conditions like Schizophrenia.

Epilepsy: Understanding Seizure Disorders

Epilepsy is one of the most common chronic neurological disorders, characterized by recurrent and unpredictable seizures due to a disorder of brain cells. Seizures occur due to sudden, uncontrolled electrical disturbances in the brain that can cause changes in behavior, movement, sensation, or loss of consciousness. It is a paroxysmal disorder. It often occurs due to too much excitation or too little inhibition.

Types of Epilepsy

Epilepsy is mainly of two types:

  1. Generalized Epilepsy
  2. Focal Epilepsy

Generalized Epilepsy

Generalized epilepsy is a type of seizure that involves abnormal electrical activity throughout the entire brain. It affects both hemispheres. It is further subdivided as follows:

  1. Tonic-Clonic Seizures
  2. Absence Seizures
  3. Tonic Seizures
  4. Clonic Seizures
  5. Atonic Seizures
  6. Myoclonic Seizures

Tonic-Clonic Seizures (Grand Mal)

Also known as Grand Mal Seizures, these are characterized by loss of consciousness, stiffening of muscles (tonic phase), and jerking movements (clonic phase). It often leads to post-seizure depression.

Absence Seizures (Petit Mal)

Also known as Petit Mal Seizures, these are characterized by a sudden loss of consciousness (for 30-60 seconds) in the middle of an activity. In this, the patient shows absent-minded behavior and it typically occurs in children.

Tonic Seizures

Tonic seizures involve sustained muscle stiffness or rigidity. They usually affect muscles in the back, arms, and legs.

Clonic Seizures

These are characterized by repeated jerking movements of muscles. They usually affect the neck, face, and arms.

Atonic Seizures

Atonic seizures involve a sudden loss of muscle control, leading to collapse or a fall.

Myoclonic Seizures

These seizures involve sudden, brief muscle contractions. They can occur in a specific muscle group or involve the entire body.