27. CNS STIMULANTS AND COGNITION ENHANCERS

Introduction

CNS stimulants and cognition enhancers (nootropics) are drugs that improve alertness, mental activity and in some cases help strengthen memory and learning. Some medicines act by increasing brain circulation and metabolism, while others raise neurotransmitter levels. These agents are useful in conditions like ADHD, narcolepsy and mild cognitive impairment.

Cognition Enhancers (Nootropics)

Nootropics are drugs that help improve learning ability, memory consolidation and recall. They are especially helpful in age-related cognitive decline, Alzheimer’s disease, head injury and memory problems due to trauma or seizures. They also protect the brain from hypoxia, hypoglycaemia and other damaging factors.

Desirable Properties of Nootropics

  • Improve learning and memory
  • Reduce memory impairment caused by ageing or drugs
  • Help information transfer between brain hemispheres
  • Improve cortical control and brain metabolism
  • Should not produce major behavioural or autonomic side effects

Common Nootropics

  • Piracetam and congeners: Aniracetam, Oxiracetam
  • Hydergine (dihydroergotoxin)
  • Vincamine, Nicergoline
  • Meclofenoxate
  • Pentoxifylline, Pyritinol
  • Cyclandate
  • Herbal: Brahmi (Bacopa), Ginkgo biloba

Mechanism of Action

Nootropics act through multiple mechanisms:

  • Improve cerebral blood flow and oxygen utilisation
  • Increase brain metabolism and ATP availability
  • Enhance cholinergic, noradrenergic and dopaminergic activity
  • Reduce excessive serotonin activity, which may improve learning
  • Protect neurons from hypoxia and excitotoxicity

Piracetam

Piracetam is a GABA derivative and the most widely used nootropic. It improves cognitive performance in elderly patients and those with memory deficits. It has minimal side effects and no significant autonomic or behavioural effects.

Uses of Piracetam

  • Age-related cognitive decline and Alzheimer’s disease
  • Learning disorders in children
  • Memory loss after trauma, seizures or alcoholism
  • Cognitive problems in neurological and psychiatric conditions

CNS Stimulants

CNS stimulants improve alertness, mood, motor activity and delay fatigue. They are used in ADHD, narcolepsy and rarely for appetite suppression. Main groups include amphetamines, non-amphetamines and methylxanthines.

Classification

  • Amphetamines/Non-Amphetamines
    • Amphetamine, Dexamphetamine, Methamphetamine
    • MDMA, Methylphenidate, Fenfluramine
    • Modafinil, Atomoxetine, Sibutramine, Pemoline
  • Methylxanthines
    • Caffeine, Theophylline, Theobromine
    • Aminophylline, Etophylline, Acebrophylline

Amphetamines and Non-Amphetamines

Mechanism of Action

These drugs enter the nerve terminal, displace stored dopamine (DA) and norepinephrine (NE), and inhibit their metabolism. This increases DA and NE levels in the synapse, leading to stimulation of the CNS.

Pharmacological Effects

  • Increased motor activity and alertness
  • Euphoria and elevated mood
  • Reduced appetite
  • Prolonged use may cause stereotyped behaviour and psychosis
  • Peripheral actions include increased BP and reduced gut motility

Clinical Uses

  1. ADHD: Methylphenidate, Dexamphetamine and Atomoxetine improve attention and control hyperactivity. Atomoxetine is non-stimulant and safer long term.
  2. Narcolepsy: Methylphenidate and Modafinil help prevent daytime sleep attacks.
  3. Obesity: Sibutramine reduces appetite but can increase BP and is contraindicated in heart disease.

Adverse Effects

  • Tolerance and psychological dependence
  • Insomnia, tremors, irritability and hypertension
  • Overdose can cause convulsions, arrhythmias, coma
  • MDMA toxicity: hyperthermia, hyponatraemia, rhabdomyolysis
  • Psychotic symptoms similar to schizophrenia

Methylxanthines

Sources

  • Caffeine – coffee, tea, cola drinks
  • Theophylline – tea
  • Theobromine – cocoa

Mechanism of Action

  • Inhibit phosphodiesterase leading to increased cAMP
  • Block adenosine receptors (adenosine causes drowsiness)
  • Reduce inflammatory gene transcription

Pharmacological Actions

  • CNS: Wakefulness, alertness, improved mental performance
  • CVS: Increased heart rate and cardiac output
  • Kidney: Mild diuretic effect
  • Respiratory: Bronchodilation and stimulation of respiratory centre
  • GI: Increased acid secretion → possible gastric irritation

Clinical Uses

  • Caffeine + analgesics for headache and migraine
  • Oral theophylline for COPD and asthma
  • Caffeine citrate for apnoea in premature infants
  • Aminophylline for acute dyspnoea in heart failure

Adverse Effects

Theophylline has a narrow safety range (8–15 μg/ml). Toxicity includes:

  • Headache, insomnia, palpitations
  • Vomiting, agitation, tachycardia
  • Arrhythmias, seizures and possible coma

Drug Interactions

  • Decrease theophylline levels: Smoking, phenytoin, carbamazepine, rifampicin
  • Increase theophylline levels: Erythromycin, ciprofloxacin, cimetidine, oral contraceptives
  • Potentiated effects with: Sympathomimetics, digoxin, diuretics, hypoglycaemic agents

Detailed Notes:

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