Analeptics are central nervous system stimulants used for conditions such as depression and respiratory depression, including drugs like doxapram and pentylene tetrazole. Doxapram acts as a respiratory stimulant by stimulating the medulla, while pentylene tetrazole blocks GABA receptor function and has convulsant properties. Both are primarily utilized in medical settings to aid in anesthetic recovery and treat emergency respiratory issues.

1. ANALEPTICS
PRESENTER – DR SABA RAZZAK
MEDICINAL CHEMISTRY
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2. ANALEPTICS
 Analeptics are central nervous system stimulants that include a wide
variety of medications used to treat depression, attention deficit
hyperactivity disorder (ADHD), and respiratory depression.
CNS STIMULANTS
CNS stimulants (CNS stands for central nervous system) are medicines that
stimulate the brain, speeding up both mental and physical processes.
They increase energy, improve attention and alertness, and elevate blood
pressure, heart rate and respiratory rate
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3. CLASSIFICATION- CNS STIMULANTS
1) ANALEPTIC STIMULANTS
2) PSYCHOMOTOR STIMULANTS( PYSCHOMIMETICS )
3) METHYLXANTHINES
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ANALEPTICS PSYCHOMIMETICS METHYLXANTHINES
Doxapram Amphetamine caffeine
Pentylene tetrazole Methamphetamine theophylline
Nikethamide Phentermine theobromine
Ethamiran Ephedirine pentoxifylline
Picrotoxin Chlorphentermine aminophylline
Strychnine Methyl phenidate

4. ANALEPTICS
RESPIRATORY STIMULANTS
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5. ANALEPTICS
 The term analeptic typically refers to respiratory analeptics.
 Capable of restoring depressed medullary functions, particularly
respiratory, and cerebral functions, such as consciousness.
 Capable of exciting the normal as well as the depressed CNS.
DRUGS include
 Doxapram
 Pentylene tetrazole
 Picrotoxin
 Nikethamide
 Ethamiran
 Strychnine
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6. CONTENTS
 INTRODUCTION
 SOURCE
 CLASS
 CHEMISTRY
 SYNTHESIS
 MECHANISM OF ACTION
 INDICATIONS
 CONCLUSION
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7. Doxapram
ANALEPTIC DRUG
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8. DOXAPRAM- INTRODUCTION
 Doxapram hydrochloride is a respiratory stimulant with a brief duration of
action, found to have a strong, dose dependent respiratory stimulant
action.
 One of the analeptic, Synthesized by Lunsford et al. (1964).
 First marketed in the USA in 1965 by Robins Company.
 SOURCE Syntheic drug
 CLASS Pyrrolidinone
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9. Appearance - Doxapram
 White to off white, colorless, crystalline powder, stable in light.
 Soluble in water, Sparingly soluble in alcohol and practically insoluble in
ether.
 Injectable products have a pH from 3.5-5.
Pharmacokinetics
 Onset: 20-40 sec
 Duration: 5-12 min (single IV injection)
 Peak Plasma Time: 1-2 min
 Half-life: 3.4 hr (2.4-4.1 hr)
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10. CHEMISTRY-DOXAPRAM 10
CLASS Pyrrolidinone derivative
IUPAC NAME 1-Ethyl-4-(2-morpholinoethyl)-3,3-
diphenylpyrrolidin-2-one
CHEMICAL FORMULA C24H30N2O2

11. Synthesis- Doxapram
 Doxapram marketed and medically used as racemate, has a stereogenic
centre.
 it possess [+] enantiomer and [-] enantiomer
 [+] enantiomer possess pharmacological activity while [-] enantiomer is
inactive.
 The doxapram can be prepared by multiple crystallization of
dibenzoyltartaric acid salts. But loss of material during crystallization is
unsuitable in industrial scale.
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Dibenzoyltartaric acid salt

12. Synthesis- Doxapram
 Three steps
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N-
allyamide
γ-lactams
Pure
Doxapram

13. Synthesis- Doxapram 13
N-allyamideγ-lactams
DOXAPRAM

14. SAR - DOXAPRAM
 A member of the class of pyrrolidin-2-ones that is N-ethylpyrrolidin-2-one
in which both of the hydrogens at the 3 position (adjacent to the carbonyl
group) are substituted by phenyl groups, and one of the hydrogens at the
4 position is substituted by a 2-(morpholin-4-yl)ethyl group.
 Pharmacophore is N-ethylpyrrolidin-2-one.
 Morpholino functional group at position 4 is essential for stimulant activity.
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15. Pharmacology- Doxapram
Mechanism of Action
 Produces respiratory stimulation in medulla (which propagates stimulation
to other parts of brain & spinal cord) through peripheral carotid
chemoreceptors.
 It is thought to stimulate the carotid body by inhibiting certain potassium
channels.
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16. Indication- Doxapram
For use as a temporary measure in hospitalized patients with acute
respiratory insufficiency superimposed on chronic obstructive pulmonary
disease.
Associated conditions---
 Anesthetic complication pulmonary
 Acute Hypercapnia
 Drug-induced Respiratory depression
 Postoperative respiratory depression
Associated Therapies--
 Post-operative respiratory stimulation
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17. Restriction- Doxapram
 Use of doxapram in the medical setting is hampered by side effects, such
as high blood pressure, panic attacks, tachycardia (rapid heart rate),
tremor, convulsions, sweating, vomiting and the sensation of "air hunger."
 Doxapram may not be used in patients with coronary heart disease,
epilepsy and high blood pressure.
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18. Pentylene Tetrazol
ANALEPTIC DRUG
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19. Pentylene Tetrazol- Introduction
 In 1924, in search of a camphor substitute, Schmidt of Heidelberg
synthesized pentylene tetrazol.
 Marketed in the same year under the trade name Cardiazol as a
cardiotonic.
 2 years later, introduced under the registered trademark of Metrazol.
 SOURCE Syntheic drug
 CLASS Tetrazole
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20. Chemistry- Pentylene tetrazol 20
Class Tetrazole derivative
IUPAC name 6,7,8,9-tetrahydro-5H- tetrazoio(l,5-
a)azepine
Chemical formula C6H10N4

21. Synthesis – Pentylene tetrazol 21
AZEPINE RING

22. SAR- Pentylene tetrazole
 Unsubstituted tetrazol has no pharmacological action, but alkylation in
position 1 or 5 leads to compounds with convulsant and analeptic
properties, or to depressant action.
 Stimulant effects are obtained with a relatively long chain substitution in
position 1 and a short chain in position 5.
 Reversal of the substituted groups causes a decrease in the stimulant
action or even depressant action.
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23.  1,5-cyclohexamethylenetetrazol and 1,5-cycloheptamethylenetetrazol
resemble pentylene tetrazol in their actions,
 whereas 1,5-cyclodecamethylenetetrazol is inactive.
 Compounds with smaller (tetra- or trimethylene) rings have low activity
which is increased by alkylation.
 The introduction of a methyl group into the pentylenetetrazol molecules
in position 8 causes an increase in activity; an isopropyl or tertiary butyl
group in the same position is even more active.
 In general, it appears that a certain number of carbon atoms is essential
for the analeptic activity.
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24. Pharmacology – Pentylene tetrazol
 Mechanism of action:
 Pentylene tetrazol acts on the entire CNS, significantly
block GABAA receptor function.
 Convulsant activity can be observed, no matter what route of
administration is used
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25. Indications – Pentylene tetrazole
 Pentylene tetrazole has been experimentally used to study seizure
phenomena.
 Found to be effective for depression.
 It has shown its convulsant actions in mice, rats, cats and primates.
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26. CONCLUSION
 CNS STIMULANTS are of three types
ANALEPTICS
PYSCHOMIMETICS
METHYLXANTHINES
 The most commonly used ANALEPTICS are Doxapram and pentylene Tetrazole.
 DOXAPRAM belongs to class pyrollidines while PTZ a Tetrazole derivative.
 Doxapram works by stimulating the medulla and PTZ by inhibiting GABA.
 Their primary medical use - As an anesthetic recovery tool.
 To treat – Emergency respiratory depression.
 As a Barbiturate antidote. ( for its poisoning/overdose)
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