Indirect acting sympathomimetic agonists:

Characters of drugs of this group:

1-They have no OH group in benzene ring; they are resistant to degradation by MAO and can be used orally.

2-They act indirect by release NE from sympathetic nerve ending.

3-Tachyphylaxis occurs with them due to depletion of NE stores.

4- Its action is potentiated by MAO inhibitors.

Differ from epinephrine in being:
1- Can be used orally.

2-Having longer duration of action.

3-Cross B.B.B, so, have more marked CNS effect.

Amphetamine It has powerful CNS stimulant actions 

Pharmacological action:

C.V.S: It raises both systolic and diastolic blood pressure. Heart rate often is reflexly slowed.

Smooth Muscles: As other sympathomimetics, it constricts the sphincter of the urinary bladder. Pain and difficulty in micturition occur.

CNS: Amphetamine is one of the most potent CNS stimulants.it produces:

1- Locomotor stimulating action: 

2-Psychic effects: Elevations of mood, self-confidence, increase the ability to concentrate; and euphoria. Performance of simple mental tasks is improved, but, the number of errors may increase.

3-Analgesic effect: It has a small analgesic effect, but it is not sufficiently to be used therapeutically. 

4-Respiration: It stimulates the respiratory center .

5-Depression of Appetite: It has been used for the treatment of obesity. 

Mechanisms of Action in the CNS:

It exerts its effects in the CNS by releasing NE from their storage sites in nerve terminals. In addition, it inhibits the neuronal dopamine transporter (DAT) (which responsible for uptake of dopamine away from synaptic cleft thus terminating the signal of the neurotransmitter), so amphetamine increase dopamine level in CNS. The vesicular monoamine transporter 2 (VMAT2) is another site of action.

Toxicity and Adverse Effects Acute toxicity:

It is extensions of its therapeutic actions, result from overdosage.

-CNS effects: restlessness, dizziness, tremor, hyperactive reflexes, irritability, weakness, insomnia, euphoria and suicidal or homicidal tendencies occur, especially in mentally ill patients.

-CVS effects: palpitation, cardiac arrhythmias, anginal pain, hypertension. -GI symptoms: dry mouth, metallic taste, anorexia, nausea, vomiting, diarrhea,
and abdominal cramps.

-Death is due to convulsions and cerebral hemorrhages.

Treatment of acute toxicity: 1-Acidification of the urine by ammonium chloride; 

2-Sedatives.

3-Severe hypertension treated by Na+ nitroprusside.

Chronic toxicity: Causes of abuse of amphetamine: usually it is used

1-By student and workers to get alert during night.

2-By athletes to increase their muscular performance and delay fatigue.

3-By many people to induce euphoria.

4-Give to horses to in races to increase their running capacity.

Therapeutic Uses It is used mainly for its CNS effects.it is used for: 1-Obesity:

2- Narcolepsy:

3-Attention-deficit hyperactivity disorder (ADHD):


Modafinil It is a new drug, it inhibits both norepinephrine and dopamine transporters, and it increases synaptic concentrations not only of norepinephrine and dopamine, but also of serotonin and glutamate, while decreasing GABA levels. 

used in treatment of narcolepsy.

Methamphetamine It is closely related to amphetamine and ephedrine. 

Methylphenidate It is related to amphetamine. It is a mild CNS stimulant with more prominent effects on mental than on motor activities. 

Ephedrine It is an agonist at both α and β receptors; in addition,

Pharmacological Actions it is effective after oral administration.