CENTRAL NERVOUS SYSTEM

STIMULANTS

By

Srota Dawn .M.Pharm(pharmacology)

CNS stimulants are the drugs whose primary action is :

1. to stimulate CNS globally

or 2. to improve specific brain functions

The CNS stimulants mostly produced a generalized action which may Produce convulsion at higher doses.

INTRODUCTION

TYPE OF DRUGS NAME OF DRUGS

ANALEPTICS PICROTOXIN,PENTYLENE TETRAZOLE,MEDAFINIL,DOXAZEPAM HYDROCHLORIDE.

METHYLXANTHINES : CAFFINE,THEOPHYLLENE, THEOBROMINE.

CENTRAL SYMPATHOMIMETIC AGENTS :

AMPHETAMINE,METHAMPHETAMINE, PHENTERMINE,BENZOPHETAMINE, FENFLURAMINE

ANTIDEPRESSANTS :

a) MONO AMINE OXIASE INHIBITORS PHENELZINE SULFATE,TRANYLCYPROMINE SULFATE

b)TRICYCLIC ANTIDEPRESSANTS IMIPRAMINE,DESIMIPRAMINE,CLOMIPRAMINE,AMITRYPTILENE

CLASSIFICATION OF CNS STIMULANTS:

ANALEPTICS :

1.The traditional analeptics are potent and non-selective.2.They can be illustrated by a)picrotoxin& b) PTZ

3.BOTH OF THEM ARE OBSOLATED NOW.4.But used in research purpose.5.Newer agents a)modafinil& b)doxapram are selective 6.These two are used in narcolepsy and as respiratory stimulant.

PICROTOXIN:

1. It exerts its effects by interfering with the inhibitory effects of GABA/at the level of GABAa receptors chloride ion channel.

2. Pharmacologically ,it has been used in determination of MOA of sedative-hypnotics and anticonvulsants.

3. Butyrolactones binds to picrotoxin site.

PENTYLENETETRAZOLE :

1.Use to determine the potency of anticonvulsants in experimental animals.

2.Acts with chloride conductance.

3. Binds with allosteric site on the GABAa receptor.

4.It is not used therapeutically now.

MEDAFINIL :

1.Wakefulness promoting properties.

2.Used to treat day time sleepness.

3.Adverse reactions: In therapeutic dose it is not severe Nervousness,anxiety,insomnia

DOXAPRAM HYDROCHLORIDE:

1.Respiratory stimulant.

2. Acts on periferal carotid receptors chemoreceptors.

3.Used in chronic obstructive pulmonary diseases

METHYLXANTHINES :

1.Caffeine is widely used as CNS stimulants.

2.Theophylline has some CNS stimulant properties ,used in bronchial asthma therapy

3.Theobromine has very little CNS stimulant property.

4.In dosage of 85 to 250 mg ,caffeine acts as cortical stimulant.

5.It facilitates clear thinking, wakefulness , promotes concentration power.

6. At higher doses convulsions may occur.

Tricyclic/ polycyclic antidepressants

mechanism of actionto block NA and 5-HT reuptakes into the

presynaptic neurons to increase NA and 5-HT level in the synaptic cleft in CNS.

Monoamine receptor densities in the brain may change over 2 to 4 week with drug use and may be important in the onset of activity.

Pharmacokinetics :

well absorbed upon oral administration, widely distributed,readily to penetrate into the CNS,long half-life,low and inconsistent bioavailability because of variable first pass metabolism in the liver. Therefore the patient response is used to

adjust dose.The initial treatment period is typically 4 to 8 weeks. The dose can be gradually reduced unless relapse occurs.

Pharmacologic effects:

All tricyclic antidepressants have similar therapeutic efficacy.

1.effects on CNS

2.cardiovascular effects

3. effects on autonomic nervous system

1. Effects on CNS

(1)A nondepressed person experiences sleepiness after administration. In addition, anxiety and toxic anticholinergic effects may be experienced.

(2)In depressed patient, tricyclic antidepressants elevate mood, improve mental alertness, increase physical activity and reduce morbid preoccupation. Onset of mood elevation is slow and requires 2 to 3 weeks after administration.

Latency period can be as long as 4 weeks.

(3)Tricyclic antidepressants can cause extrapyramidal symptoms and ataxia. High doses of tricyclic antidepressants are capable of producing seizures and coma.

2.cardiovascular effects :

orthostatic hypotension, arrhythmias, tachycardia, slow atrioventricular conduction.

3.Effects on autonomic nervous system :

anticholinergic effect.

Therapeutic uses:

1. severe endogenous depression.

2. enuresis(bed-wetting): imipramine.

3. obsessive-compulsive neurosis accompanied by depression, and phobic anxiety syndromes, chronic pain, and neuralgia may respond to tricyclic agents.

Adverse effects:

Adverse effects of tricyclic anti-depressants resemble to phenothiazines.

1.peripheral effects: anticholinergic actions2.central effects: ataxia, dizziness and muscle tremor; manic

excitement and delirium can occur in the patients with bipolar illness.

3. cardiovascular effects: cardiac arrhythmias and hypotension

MAO inhibitors

MAO inhibitors inhibit MAO activity to increase store of noradrenaline, serotonin and dopamine within the neuron.

MAO inhibitors are indicated for depression patients who are unresponsive or allergic to tricyclic antidepressants or who experience strong anxiety.

Selective 5-HT reuptake inhibitors

The selective 5-HT reuptake inhibitors specially inhibit serotonin reuptake. Compared with tricyclic antidepressants, these drugs cause fewer anticholinergic effects and lower cardiotoxicity.

References :

1.Wilson & Gisvold’s Organic Medicinal and Pharmaceutical chemistry

2.Essentials of Medical Pharmacology-KD TRIPATHY

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