Pharmacological actions of CNS Stimulants

1. Sreenu Thalla
Associate Professor
Department of Pharmacology

2. • Stimulants are a substance which tends to increase behavioral activity
when administered
• ”Psychomotor stimulants cause
 Excitement
 Euphoria
 Decrease feeling of fatigue
 Increase motor activity

4. Signs and Symptoms
• Elevate Mood
• Increase Motor Activity
• Increase Alertness
• Decrease need for Sleep
• In case of overdose lead to convulsion and death.

5. Therapeutic Indications
• Obesity (anorectic agents)
• Attention Deficit Hyperactivity Disorder (ADHD); lack the ability
to be involved in any one activity for longer than a few minutes.
• Narcolepsy: It is a relatively rare sleep disorder, that is
characterized by uncontrollable bouts of sleepiness during the
day.

9. • Block neurotransmitter reuptake (Most reuptake inhibitors
affect either NE or 5HT) e.g. Tricyclic antidepressants, Cocaine,
Selective Serotonin reuptake inhibitors
• Promote Neurotransmitter Release – Phenylethylamines and
related compounds. Amphetamine, Methylphenidate.
• Block Metabolism - MAO inhibitors
Mechanism of action of CNS Stimulants

10. Amphetamine
• Block the reuptake of norepinephrine and dopamine into the
presynaptic neuron and increase the release of these monoamines into
the extraneuronal space

11. Adverse effects
• Endocrine metabolic
 Weight loss (4-9%, pediatric; 11%, adults)
• Gastrointestinal
 Abdominal pain (11-14%, pediatrics)
 Loss of appetite (22-36%)
 Xerostomia (35%)
• Neurologic
 Headache (26%)
 Insomnia (12-17% pediatric; 27%, adults )
• Psychiatric
 Feeling nervous (6%)

12. Pharmacodynamics
• Ampthetamine increased the activity of monoaminergic system.
• The primary mechanism is by releases of dopamine from the nerve
terminals.
• Ampthetamine are thought to enter the nerve terminal via the
transporters, distrupt the storage vesicles of dopamine and reverse
the direction of dopamine.

13. Pharmacokinetics
• Amphetamine may administer through orally, intranasally,
intravenosly.
• The peak response occur 1 to 3 hrs after oral administration and
approximately 15 min after injection.
• A single dose maintain an effect for up to 7 to 12 hrs.
• The half life may increases 18 to 34 hrs.

14. Contraindications
• Hyperthyroidism
• Hypertension
• Arterioselerosis
• Manic behaviour
• Psychotic disorder
• Drug abuse
• Suicidal thoughts
• Agitation

15. Indications
• Attention deficit Hyperkinetic disorder
• Parkinsonism
• Narcolepsy
• Obesity
• Epilepsy
• Euphoria

16. Methylphenidate
• It has CNS stimulant properties similar to those of amphetamine
and may also lead to abuse, although its addictive potential is
controversial.
• It is taken daily by 4-6 million children in the USA for ADHD.
• Methylphenidate is a more potent dopamine transport inhibitor
than cocaine, thus making more dopamine available.
• It has less potential for abuse than cocaine, because it enters the
brain much more slowly than cocaine and, does not increase
dopamine levels as rapidly.

17. Non-Therapeutic CNS stimulants (Seizure Inducers)
• Strychnine & Picrotoxin
• Strychnine - Inhibits glycine receptors
• Picrotoxin - Acts on the chloride ion channel associated with GABA
receptors.
• Bemegride - Barbiturate Antagonist
• Pentylene tetrazole - Na+/K+ channel blocker ?Increases cholinergic
activity.

18. Xanthines
Mechanism(s) of action
• Inhibition of cAMP phosphodiesterase
• Competitive inhibitor of adenosine
• Promote NE release
• Promote intracellular Ca+2 release
• The order of potency for CNS activity is
• Caffeine > Theophylline > Theobromine
• Theophylline is used for maintenance treatment of asthma with some
side effects

19. Nicotine
• Nicotine is a potent parasympathomimetic alkaloid found in the family
of plants (Solanaceae) that acts as a nicotinic acetylcholine receptor
agonist
• Nicotine is the active chemical constituent in tobacco
• As nicotine enters the body, it is distributed quickly through
the bloodstream and crosses the blood–brain barrier reaching
the brain within 10–20 seconds after inhalation
• Nicotine is available in many forms including cigarettes, cigars, chewing
tobacco, and smoking cessation aids such as nicotine patches, nicotine
gum and electronic cigarettes.
• Nicotine is used widely throughout the world for its stimulating effects

20. Adverse Reactions
• GIT effects are the most common; abdominal pain and nausea.
• In seizure patients, methylphenidate seems to increase the seizure
frequency, especially if the patient is taking antidepressants.