Libyan International Medical University

Faculty Of AMS
3RD Year AMS (2021-2022)
Block II: NS
Week VI: Pharmacology Lect.

CNS Stimulants
Dr. Hwuida Khattab Elhassi (PhD
Pharmacology)
ILOs:
 Outline the general effect of CNS stimulants
 Classify CNS stimulants
 Enumerate drugs classified as Psychomotor stimulants and list their effects
 List Methylxanthines, explain their mechanism of action, effects and clinical uses
 List central and peripheral effects of Nicotine.
 List amphetamine related drugs, explain their mechanism of action, effects and
clinical uses
 List Psychotomimetic drugs and outline the difference between them and
stimulants drugs.
 Outline mechanism of action and effects of Lysergic Acid Diethylamide.
 Outline mechanism of action, effects and therapeutic uses of Tetrahydrocannabinol
 Explain mechanism of action, effects and therapeutic uses of Cocaine.
CNS Stimulants:
 Drugs that increase the chemical and electrical activity of
the CNS and make the user more alert, active, anxious,
restless and in general more stimulated than normal.
 Are drugs which increase the muscular (motor) and the
mental (sensory) activities.
 Their effects vary from the increase in the alertness and
wakefulness (as with caffeine).
 To the production of convulsion ( as with strychnine) or
death due to over stimulation
CNS Stimulants:
 Don’t have specific action.
 Excessive stimulation of CNS is followed by depression.
 Not therapeutically useful.
 Some are used as analeptics.

General Signs & Symptoms of CNS Stimulation:

1. ↑ Heart rate
2. ↑ Respiratory rate
3. Instability
4. Tremors
5. Hair erection
6. Convulsion. 
Molecular Basis of CNS Stimulation:
 Imbalance between inhibitory and excitatory processes as
in the brain.
 Hyper-excitability of neurons results from:
 Potentiation or enhancement of excitatory
neurotransmission (e.g. amphetamine)
 Depression or antagonism of inhibitory transmission (e.g.
Strychnine & picrotoxin)
 Block neurotransmitters reuptake (Most reuptake inhibitors
affect either NE or 5- HT(Serotonin): Cocaine
 Block Metabolism - MAO inhibitors: ex. Phenelzine.
Classification of CNS Stimulation:
 According to:
 Structural similarities.
 Site of therapeutic action in the central nervous system
(CNS).
 Major therapeutic usages/ Actions.
According to their site of action.:
 Cerebral stimulants or cortical stimulant (amphetamines,
caffeine, theophylline, aminophylline)
 Medullary stimulants: Analeptic (picrotoxin, nikethamide, ,
Amiphenazole, bemegride, pentylenetetrazole)
 Spinal stimulants (strychnine)
 Stimulate CNS reflexes. (Lobeline, ammonia, nicotine
 
Classification of CNS Stimulation:
I. Psychomotor stimulants.
II. Psychotomimetic drugs (Hallucinogens)
III. Convulsants & respiratory stimulants:

There are a few indications for the medical uses of these

agents but they are popular as recreational drugs.
Classification of CNS Stimulation:
 Psychomotor stimulants
 Temporal improvement in mental or physical function or
both.
 Cause excitement, euphoria, relieve fatigue and increase
motor activities.
 Methylxanthines (theophylline, theobromine, caffeine)
 Nicotine
 Varenicline (Partial agonist: nicotine)
 Cocaine
 Amphetamine & Methamphetamine.
 Dextroamephetamine
 Methylphenidate
Classification of CNS Stimulation:
 Psychomotor stimulants

 M.O.A:
 Releases MA at synapses in the brain and spinal cord.
 Inhibits neuronal uptake of MA.
 Direct agonist of DA & 5-HT receptors.
 Antagonist at certain adrenoceptors.
 Inhibition of MAO.
Psychomotor Stimulants: Amphetamines
 Potent CNS Stimulant.
 Diminish the awareness of fatigue.
 Depress appetite.
 M.O.A:
 Stimulate MA release into the synapses.
 Sympathomimetic drug CNS& peripheral.
Psychomotor Stimulants: Amphetamines
 CNS effects:
 Wakefulness & Euphoria
 Increase alertness & decrease fatigue
 Slight analgesic effect
 Loss of appetite

 CNS effects:
 Peripheral:
 Increase HR & BP
 Urinary retention
 N, V & GIT up set.
Psychomotor Stimulants: Amphetamines
 Clinical uses:
 Narcolepsy (Modaphenil) or methylphenidate.
 Attention deficit hyperactivity disorder (Methylphenidate).
 obesity.

 Adverse effects:
 CNS: Euphoria, dizziness, tremor, irritability, insomnia, hallucination,
anxiety, convulsion (at high dose), hyperthermia and coma.

 psychotic reactions which often misdiagnosed as Schizophrenia,

 CVS: cardiac stimulation  headache, Increase HR & BP, palpitation,

arrhythmia & angina pain.

 Others: weight loss, bladder pain, abdominal cramps & GIT upset.

 Addiction; psychotic dependence, tolerance and physical dependence.

Psychomotor Stimulants: Amphetamines
 Amphetamine Derivatives:
 Dextroamphetamine.
 Lisdexamfetamine (Prodrug of Dextroamphetamine.)

 Methamphetamine: stronger, quicker & more addicting.

 Modafinil: used in sleep disorders.

 Fenethylline: Prodrug amphetamine + theophylline, most abused in

Arab countries.

 Methylphenidate: less side effect.

Psychomotor Stimulants: Amphetamines
 Abuses:
 Cognitive enhancer & euphoria.

 Drug interactions:
 TCA.
 Antihypertensive.
 Food high in tyramine content.
Psychomotor Stimulants: Methylphenidate
 More potent DA elevator.

 Therapeutic uses:
 Attention deficit hyperactivity disorder (ADHD).
 Narcolepsy.

 Adverse Reactions:
 Most common: Abdominal pain, nausea and anorexia.
 Insomnia, irritability, increase seizure frequency in patient with a
seizure disorder.
Psychomotor Stimulants: Nicotine
• Alkaloid.
• Active ingredient in tobacco.
• Second most widely used after caffeine
• Not used therapeutically except in smoking cessation
• Serious risk factor for lung, CVS, cancers & other illness.

 M.O.A:
• Nicotinic receptors
• Low doses: + autonomic ganglia (Ganglionic
stimulation).
• High doses: Prolonged stimulation  desensitization 
block autonomic ganglia (Ganglionic blockade).
• In CNS: +Nicotinic receptors  stimulant effect.
Psychomotor Stimulants: Nicotine
 Pharmacokinetics:
• Highly lipid soluble well absorbed via oral mucosa, lungs, GIT
mucosa and skin.
• Distribution: BBB, Placenta & milk.
• Metabolism: Lung & Liver
• Elimination: renal.

 CNS effect: Cross BBB

• Low dose: Euphoria, relaxation, improve attention, learning problem
solving, appetite suppresser.
• High doses: central respiratory paralysis and sever hypotension
(medullary paralysis.

 Peripheral effect:
• Sympathetic stimulation: + AD &NA  + COP &PR +BP
9Vasoconstriction)
• Parasympathetic stimulation: + intestinal motility & all secretions.
Psychomotor Stimulants: Nicotine
 S/E:
• High doses: Sympathetic & Parasypathetic blockade 
hypotension & GIT activity ceases.
• High doses: irritability, tremer, intestinal cramps, diarrhea, increased
HR & BP.
• Lethal doses: 30-60mg: respiratory failure.

 Withdrawal:
• Rapid onset.
• Irritability, anxiety, restlessness, difficulty concentrating,headache,
insomnia

 Smoking cessation program: to control Withdrawal symptoms

• Nicotine replacement therapy: Varenicline, Bupropion or other anti
depressant.
• Behavioural therapy
Psychomotor Stimulants: Nicotine
 Smoking cessation program: to control Withdrawal symptoms
• Nicotine gum, transdermal patch

• Enzyme inducer
Psychomotor Stimulants: Cocaine
• Coca plant alkaloid  highly lipid soluble.
• HCl salt  water soluble.
• Different forms.
• Highly addictive (Euphoria)
• Local aesthetic.
• Only LA  VC Ncrosis & Perforation of the nasal septum
(chronic inhation of cocain powder)

 M.O.A.:
• SNRIs
• Na-channels blocker
Psychomotor Stimulants: Cocaine
 Pharmacokinetics:
 Large Vd, quick metabolism.
 Principle metabolites:
 Ecogonine methylester (Inactive).
 Benzoylecogonine (inactive)
 Norcocaine (Active).
 T1/2 : 4-6hrs
 Excreted in urine: Benzoylecogonine is detectable 1-36 days while
cocaine is detectable for a few hrs
 Rout of administration:
 Chewing, sniffing, Oral, Smoking, IV.
Psychomotor Stimulants: Cocaine
 Action:
• Well being.
• Euphoria: high dose replaced with restlessness, sleeplessness,
nervousness, hallucinations & delusion.
• Increase attention, sexual excitement, promote talkativeness, enhance
mental alertness and learning.
• Increase HR & BP.
• Increase body temp.
• Mydriasis & light sensitivity.
Psychomotor Stimulants: Cocaine

 S/E. Overdose:
• Agitation, enhance reflexes and headache.
• Tachycardia & irregular respiration
• Rise in temp. N & V.
• Hallucination, convulsion, delirium &seizure
• Stroke & cerebral haemorrhage
• Heart failure & death for respiratory failure

• Powerful addictive & abused drug with withdrawal symptoms.

Psychomotor Stimulants: Methylxanthines

 Caffeine, Theophylline & Theobromine

 M.O.A:
1. - PDE  +cAMP & cGMP SM & Heart
2. Block Adenosine receptor: Heart & Brain
3. Translocation of extracellular Ca+2.

 Pharmacokinetics:
1. Well absorbed orally
2. Widely distributed
3. Metabolized by CYP1A2
4. Excreted by kidney
Psychomotor Stimulants: Methylxanthines
 Actions: (Caffeine, Oral)
 50-250mg:
• decrease Fatigue & drowsness
• Increase mental alertness (cerebral cortex stimulation)
• Not harmful in patients with coronary disease
• +ve inotropic & +ve chronotropic
 400>
• Safe for most health adults
• harmful in patients with coronary disease

 500-600
• +ve inotropic & +ve chronotropic ( Direct stimulation of
myocardium)
• Excitement, delirium & chronic seizure.
Psychomotor Stimulants: Methylxanthines
 1.5g:
• Anxiety & tremors
• Tcchycardia & arrhythmia , peripheral VD  -BP (Acute
adminstration).
• Cardiac arrest.
• Death due to arrhythmia. (Lethal dose)

 S.M.:
• Vascular S.M.Relaxation.
• Bronchial S.M.

 Miscellaneous;
 Xanthines  shorten the clotting time due to increasing tissue
prothrombin and factor V.

 
Psychomotor Stimulants: Methylxanthines
 Mild diuretic effects:
• (Theophylline)
• - Na reabsorption
• + renal blood flow.

 Bronchodiatation
 + Gastric acid secretion (Caffeine)
 Tolerance & withdrawal symptoms (fatigue & sedation)

 
Psychomotor Stimulants: Methylxanthines
 Uses:
• CNS stimulation (Reverse hypnotics).
• Bronchial asthma, COPD
• Headache (+ NSAID/Paracetamol)
• Migraine headache (+ ergotamine)
• Coronary Vasodilation.
• Diuretic.
• Neonatal apnoea syndrome.
Psychomotor Stimulants: Methylxanthines
 S/E:
• Moderate: Insomnia, anxiety & agitation.
• High toxic dose: Delusion, Emesis & convulsion
• Lethal dose (10g): Cardiac arrhythmias.
• Caffeine withdrawal symptoms (routinely consumption of >
600mg/day): sleepiness, irritability & headache (up to 1week)
• Tolerance, psychiatric dependence and habituation.
• Epigastric pain & ulcer (stimulate gastric secretions).
• Transient diuretic effect & Vomiting  Dehydration in children.
Psychomotor Stimulants: Methylxanthines
 Drug interactions:
• Theophylline (Low therapeutic index)
• Enzyme inducers ;Phenytoin & Barbiturates, smooking
• Enzyme inhibitors: Ketoconazole, Cimetidine &
Erythromycin (Macrolides).
 Precaution:
• Slow infusion.
• Arrhythmia.
• Sever renal, hepatic & pulmonary diseases.
Classification of CNS Stimulation:
 Psychotomimetic drugs (Hallucinogens):
 Produce hallucinations: Altering the perception of the
surrounding.
 Similar to dream while being awake.
 Has no therapeutic uses.
 Altering the mood
 Produce changes in thought patterns and mood
 LyserLysergic acid diethylamide (LSD): Serotenin.
 Tetrahydrocannabinol (THC)
 Phencyclidine
 Scoplamine & Atropine: Ach
Psychotomimetic Drugs: Hallucinogens
 Psychogenic: mimic the action of psychosis
 Widely illegally abused.

 Lysergic Acid Diethylamide: (LSD)

 Powerful agent  temporal psychosis

 M.O.A:
 Partial agonist on 5HT2A in the mid brain
 Modulate NMDA receptors
 CNS Actions: Massive increase in neuronal activity in some brain
regions.
 Hallucination, altered mental state, temporal psychosis, delusion,
body image & time changes, impaired perception.
 Bad trip (fear, terrifying thoughts, losing of control_
 Flashbacks.
 Long lasting psychosis.
Psychotomimetic Drugs: Hallucinogens
 Peripheral Actions:
 Tachycardia, HTN, Mydriasis, sweating, loss of appetite, dry mouth,
tremor, piloerection.

 Phencyclidine:
 Inhibit reuptake of Dopamine, NE, SER
 Anticholinergic but induce hyper salivation.
Psychotomimetic Drugs: Tetrahydrocannabinol
 M.O.A.:
 CB1  - Dopamine neurons

 CNS ACTION.:
 Felling of well being, relaxation & euphoria
 Disorientation and lack of concentration.
 Impaired learning & memory.
 Impaired thoughts and expression
 Drowsiness, sedation and mood changes
 Fight thoughts, dulling attention and psychosis.

 Peripheral ACTION.:
 +HR & BP
 Eye redness
 Red. IOP
 Dry mouth & throat
 Increase appetite.
Psychotomimetic Drugs: Tetrahydrocannabinol
 S/E.:
 Fatigue, paranoia, psychosis, memory & mood problems
 Slurred speech & dizziness
 Urinary retention & constipation
 Lung damage, CVS & IMM effects.

 Drug interactions.:
 Cocaine & amphetamine  increase HTN & cardiotoxicity
 BDZs, barbiturates, ethanol, opioids and antihistamines 
drowsiness & CNS depression..
Classification of CNS Stimulation:

 Convulsants & respiratory stimulants:

 Doxapram, nikethamide
 Have no clinical applications.
 Research: Picrotoxin & Strychnine

 
Consultants & respiratory stimulants:
 Doxapram, nikethamide
 Research: Picrotoxin & Strychnine

 Action:
 Brain stem & Medulla  + respiratory centre.
 Large dose  Convulsion

 Uses:
 Narcotic Poison.
 Post anaesthesia.

 S/E:
 HTN, Tachycardia, arrhythmia, convulsion.
 Reference:
•Rang and Dal’s Pharmacology (6th Edition):
•Katzung B. G.,(2019), Basic & clinical
pharmacology, 14th ed.