Stimulants are substances that increase behavioral activity when administered. They are classified as psychomotor stimulants or hallucinogens. Psychomotor stimulants like cocaine, amphetamines, and nicotine cause excitement, euphoria and increased motor activity by increasing the neurotransmitters dopamine and norepinephrine. Hallucinogens affect thought patterns and mood but have little effect on the brain stem and spinal cord. Common stimulants include caffeine, nicotine, cocaine, amphetamines, and methylphenidate.

1. 1

2.  Defination
“Stimulants are a substance which
tends to increase behavioral
activity when administered”

3. Few clinical uses, Important as drugs of abuse.
Factors that limit the therapeutic usefulness include:
1.Dependence: Psychological and physiological.
2.Tolerance to the euphoric and anorectic effects
are classified according to their action into:
Psychomotor stimulants
Hallucinogen (psychotomimetic or psychedelics) drugs
3

4. 1. Psychomotor stimulants
cause: Excitement, Euphoria, Decrease feeling of fatigue
& Increase motor activity
Ex., Methylxanthines (caffeine, theobromine, theophylline), nicotine,
cocaine, amphetamine, atomoxetine, modafinil, methylphenidate.
2. Hallucinogens (psychotomimetic):
Affect thought, perception, and mood, therefore produce
profound changes in thought patterns & mood,
little effect on the brain stem & spinal cord
Ex., Lysergic acid diethylamide (LSD), Phencyclidine (PCP),
Tetrahydrocannabinol (THC), Rimonabant.
4

5. Q. What are Stimulants?
Answer. Chemical stracture are similar to
monoamine neurotransmitters. All are indirect-
acting sympathomimetics:
1. Many CNS stimulants release catecholamines,
Therefore, their effects are abolished by prior treatment with reserpine or
guanethidine
Ex: amphetamine, dextroamphetamine,
methamphetamine, methylphenidate (Ritalin),
ephedrine, pseudoephedrine (a stereoisomer of
ephedrine), tyramine.
2. Other CNS stimulants block the reuptake of
catecholamines (NE and DA) and serotonin:
EX. Cocaine, sibutramine (reduct)®
, modafinil
5

6. 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. It is sometimes accompanied by
catalepsy, a loss in muscle control, or even paralysis
brought on by strong emotion, such as laughter.
Contraindications: patients with anorexia, insomnia,
asthenia, psychopathic personality, a history of
homicidal or suicidal tendencies.
6

7. I. Cocaine, Crack (free base or hydrochloride).
II. Amphetamines:
D-Amphetamine, Methamphetamine, methylphenidate
(use to treat attention deficit disorders in children),
phenmetrazine (Preludin) - used to treat obesity,
III. Methylxanthines: caffeine (coffee), theophyline
(tea), theobromide (chocolate).

8.  Alkaloid from Erythroxylon coca
 Indigenous to western South America
 Coca leaves used for religious, mystical,
social, stimulant, and medicinal purposes
 Main stimulant uses: endurance, feeling of
well-being, alleviate hunger
 Medical uses: local anesthetic,
vasoconstrictor

9.  alertness/vigilance, concentration
 mental acuity, sensory awareness
 euphoria/elevated mood
 brain electrical activity
 self-confidence, grandiosity
 need for sleep (insomnia)
 appetite
 brain blood flow, glucose metabolism
London et al., 1999

10.  sexual desire, but cocaine can  performance
 anxiety, suspiciousness
 convulsions, tremor, seizure
 psychosis, delirium
 locomotion at low/moderate doses
 repetitiveness, stereotypy at high doses
 reinforcement/addiction
 judgement, complex multi-tasking

11.  Blood pressure
 Blood sugar
 Heart rate
Irregular heart beat
Vasoconstriction
 Body temperature
Bronchodialation
& Impaired breathing
Fight/Flight/Fright Syndrome
(sympathetic nervous system arousal)

12.  Routes of administration
◦ Insufflated (snorted)
◦ IV (mainlined)
◦ Inhaled (freebased)
◦ Oral

14.  Cocaine has a local anesthetic action
that represents the only current
rationale for the therapeutic use of cocaine.
 For example, cocaine is applied topically as a
local anesthetic during eye, ear, nose, and
throat surgery.
 Whereas the local anesthetic action of cocaine
is due to a block of voltage-activated sodium
channels, an interaction with potassium
channels may contribute to the ability of
cocaine to cause cardiac arrhythmias.

15.  Both cocaine and amphetamines penetrate BBB
easily
 Half-lives
◦ Cocaine: ~ 50-90 min
◦ Amphetamine: ~ 5-10 hours
◦ Meth: ~ 12 hours
 Metabolites include active and inactive compounds
 Cocaine is unusual in that it “autometabolizes” in
the blood in addition to normal liver metabolism.
◦ Cocaine ----> norcocaine, ecgonine methyl ester, benzoylecgonine

16.  High abuse potential
 Physical and psychological dependence
 Tolerance to euphoria, appetite suppression;
sensitization to psychomotor
 Withdrawal
◦ Physically mild to moderate (hunger, fatigue, anxiety, irritability,
depression, panic attacks, dysphoric syndrome)
 Dysphoric syndrome (1-5 days after the crash): characterized by
decreased activity, amotivation, intense boredom and anhedonia,
intense “craving” for cocaine. May last 1-10 weeks.
 Intense cravings
 Route of administration important to addiction risk

17.  Synthetic analog of ephedrine,
active ingredient in mahuang
 Mahuang used in China for
asthma
◦ Chinese (Mandarin) má huáng : má,
hemp + huáng, yellow
 Methamphetamine and
Methylphenidate (Ritalin) are
very similar
 Medical uses: obesity, ADHD,

18. Amphetamine is a noncatecholaminergic
sympathetic amine that shows neurologic and
clinical effects quite similar to those of cocaine.
Dextroamphetamine is the major member of this
class of compounds.
Methamphetamine is a derivative of amphetamine
that can be smoked, and it is preferred by many
abusers.

20.  Adverse effects:
 - Cardiovascular: Hypertension (7% to 22%,
pediatric )
 - Endocrine metabolic: Weight loss (4% to
9%, pediatric; 11%, adults )
 - Gastrointestinal: Abdominal pain (11% to
14%, pediatrics ), Loss of appetite (22% to 36%),
Xerostomia (35% )
 - Neurologic: Headache (26% ), Insomnia ‫ارق‬
)12 % to 17%, pediatric; 27%, adults )
 - Psychiatric: Feeling nervous (6% )

22.  After injecting, the mice with amphetamine you
well notice:
- Hair erection
 - Licking, gnawing.
 - Stereotype
 - Sniffing

23. Methylxanthines
 The methylxanthines include theophylline which
is found in tea; theobromine found in cocoa;
and caffeine .
 Caffeine, the most widely consumed stimulant
in the world, is found in highest concentration in
coffee, but it is also present in tea, cola drinks,
chocolate candy, and cocoa.

24. Several mechanisms have been proposed
for the actions of methylxanthines,
including translocation of extracellular
calcium, increase in cyclic adenosine
monophosphate and cyclic guanosine
monophosphate caused by inhibition of
phosphodiesterase, and blockade of adenosine
receptors.
The latter most likely accounts for the actions
achieved by the usual consumption of caffeine-
containing beverages

25.  CNS: The caffeine contained in one to two
cups of coffee causes a decrease in fatigue
and increased mental alertness as a result of
stimulating the cortex and other areas of the brain.
 Consumption of 1.5 g of caffeine (12 to 15 cups of
coffee) produces anxiety and tremors.
 The spinal cord is stimulated only by very high doses
of caffeine.
 Tolerance can rapidly develop to the stimulating
properties of caffeine; withdrawal consists of feelings
of fatigue and sedation.

26.  Cardiovascular system:
 A high dose of caffeine has positive inotropic and
chronotropic effects on the heart.
 Diuretic action:
 Caffeine has a mild diuretic action that increases
urinary output of sodium, chloride, and potassium.
 Gastric mucosa:
 Because all methylxanthines stimulate secretion of
hydrochloric acid from the gastric mucosa,
individuals with peptic ulcers should avoid
beverages containing methylxanthines

28. The methylxanthines are well absorbed
orally.
Caffeine distributes throughout the body,
including the brain.
The drugs cross the placenta to the fetus and is
secreted into the mother's milk.
All the methylxanthines are metabolized in the
liver,
generally by the CYP1A2 pathway, and the
metabolites are then excreted in the urine.

29.  Moderate doses of caffeine cause
insomnia, anxiety, and agitation.
 The lethal dose is about 10 g of caffeine (about
100 cups of coffee), which induces cardiac
arrhythmias; death from caffeine is thus highly
unlikely.
 Lethargy, irritability, and headache occur in
users who have routinely consumed more than
600 mg of caffeine per day (roughly six cups of
coffee per day) and then suddenly stop.

30. Nicotine is the active ingredient in
tobacco.
Although this drug is not currently used therapeutically,
nicotine remains important, because it is second only
to caffeine as the most widely used CNS stimulant
and second only to alcohol as the most abused drug.
 In combination with the tars and carbon monoxide
found in cigarette smoke, nicotine represents a
serious risk factor for lung and cardiovascular
disease, various cancers, as well as other illnesses.
Dependency on the drug is not easily overcome.

31.  In low doses, nicotine causes ganglionic
stimulation by depolarization.
 At high doses, nicotine causes ganglionic
blockade.
 Nicotine receptors exist at a number of sites in the
CNS, which participate in the stimulant attributes of
the drug.

32.  Nicotine is highly lipid soluble and readily
crosses the blood-brain barrier.
 Cigarette smoking or administration of low
doses of nicotine produces some degree of
euphoria and arousal as well as relaxation.
 It improves attention, learning, problem solving,
and reaction time.
 High doses of nicotine result in central respiratory
paralysis .

33. Because nicotine is highly lipid soluble,
absorption readily occurs via the oral
mucosa, lungs, mucosa, and skin.
Nicotine crosses the placental membrane and is
secreted in the milk of lactating women.
By inhaling tobacco smoke, the average smoker takes
in 1 to 2 mg of nicotine per cigarette (most cigarettes
contain 6 to 8 mg of nicotine). The acute lethal dose
is 60 mg. More than 90 percent of the nicotine
inhaled in smoke is absorbed.

34.  The CNS effects of nicotine include
irritability and tremors.
 Nicotine may also cause intestinal
cramps, diarrhea, and increased heart rate and
blood pressure.
 In addition, cigarette smoking increases the
rate of metabolism of number of drugs.