CNS Stimulant Drugs

322 PHL33rd rd Lecture Lecture T.A Samiah

King Saud UniversityCollege Of PharmacyDepartment of Pharmacology

pharmacological experiments

In vitro

Isolated tissue

Adv:

determination exact MOA & the potency of the drug

In vivo

Whole animal or intact animalAdv: observation of the clinical effect of drugs

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Anatomy of The Brain

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Anatomical features of CNS

Cerebellum+Pons → Equilibrium & coordination of movement

Medulla oblongata → contain vital center e.g. respiratory and cardiovascular centers

Spinal cord → Responsible for all reflexes

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Classification of Drugs Acting on CNS

Drugs acting on

CNS

CNS stimulants

CNSdepressants

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CNS Stimulants

Definition: They 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) and sometimes lead to death due to over stimulation.

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Classification of CNS stimulants:

Cerebral stimulants.

Psychomotor stimulants e.g. Amphetamine

Medullary stimulants.

Psychotomimetic stimulants (hallucinogenic drugs) e.g. Cannabis, LSD (lysergic acid diethylamine), THC

(tetrahydrocannabinol).

Spinal cord stimulants.

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General Signs & Symptoms of CNS Stimulation

1. ↑ Heart rate2. ↑ Respiratory rate3. Instability & restlessness4. Muscle twitching (tremors) 5. Hair erection6. Convulsion

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Classification of CNS Stimulants According to Their Site of action

1. Cerebral stimulants2. Brain stem ( Pons & medulla) stimulants3. Spinal cord stimulants

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1 -Cerebral Stimulants

ExamplesExamplesCaffeine & CocaineCaffeine & Cocaine

Site of the action

Cerebral cortex

MOA1.1. It inhibits phosphodiesterase enz. → ↑ cAMP It inhibits phosphodiesterase enz. → ↑ cAMP

↑calcium in CNS & heart→ excitation→ excitation

↓calcium in Smooth muscles→ → relaxationrelaxation

2. A2A2 receptors antagonist → CNS stimulation & receptors antagonist → CNS stimulation & smooth muscles relaxation smooth muscles relaxation

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1 -Cerebral Stimulants

End point1.1. Hair erectionHair erection

2.2. Tail erection (onset of action)Tail erection (onset of action)

High Doseepileptiform type of convulsionepileptiform type of convulsion

Removed byDecapitation & Pithing

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2 -Medullary Stimulants

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Example Picrotoxin, Coramine ,Cardiazole

Site of the actionMedulla oblongata

MOA of ( picrotoxin )

1- Non-competitive GABAA antagonist2 -Block Cl- channel associated with GABAA

receptors lead to blocking the postsynaptic inhibitory effect of GABA. So, no hyper-polarization . →excitation→excitation

End pointClonic convulsion

Removed byDecapitation

3-Spinal Cord Stimulants

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Example Strychnine

Site of the action

Spinal cord

MOA 1- Block the postsynaptic inhibitory response to glycine by blocking glycine receptors in spinal cord .glycine is the main inhibitory transmitter acting on motor neurons

End pointtonic convulsion

Removed byPithing

Differences Between Clonic & Tonic Convulsions

ClonicTonic

-Produced by ↑dose of medullary stimulants

- Asymmetric(when the left side of the body convulsed the right side relaxed)

- Coordinated (when the flexors contract the extensors relaxed)

- Spontaneous in origin(convulsion develop by its own)

- Intermittent

- Removed by decapitationIt starts as clonic then converted into tonic-clonic and finally to tonic.

-Produced by ↑dose of spinal cord stimulants

- Symmetric(both sides convulsed at the same time)

-uncoordinated (both flexors and extensors contract)

- Reflex in origin (need for external stimuli)

- Continuous

- Removed by pithing- Opisthatenous Posture”(Arched Back

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Opisthatenous posture

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Lab work

DrugConcDoseROA

Caffeine 1% 100 mg/kg

IP

Strychnine 0.1% 5 mg/kg IP

Picrotoxin 0.5% 25 mg/kg IP

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Calculation

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