Barbiturates

Khalid Hussain
Khalid HussainProfessor um University of the Punjab
Sedatives and Hypnotics
 Sedative: Calm down, treat agitation
 Hypnotic: Induce sleep
    go to sleep fast, feel fresh when awake
 Anxiolytic: Reduce anxiety
    physical, emotional, cognitive
Barbiturates
Barbiturates
• Derivatives of Barbituric acid or Malonylurea: Combination of urea and
  malonic caid
• Depressants of the central nervous system, impair or reduce activity of the
  brain by acting as a Gamma Amino Butyric Acid (GABA) potentiators
• Produce alcohol like symptoms such as ataxia (impaired motor control),
  dizziness and slow breathing and heart rate
History
•   Barbituric acid was first preraed in 1864 by a German scientist - Adolf von
    Baeyer - by combining urea from animals and malonic acid from apples
•   Its first derivative utilized as a medicine was used to put dogs to sleep, latter
    Bayer produced Veronal in 1903 to be used as a sleeping aid
•   Soon after, phenobarbital and many other barbituric acid derivatives were
    discovered and marketed
    Interesting facts
•   Caused the death of many celebrities such
    as Jimi Hendrix and Marilyn Monroe
•   Used by the Nazis during WWII for
    euthanasia
Types




               Barbituric Acid




Amobarbital   Phenobarbital      Pentobarbital
Synthesis




        Malonic Acid   Urea          Barbituric Acid



Barbituric acid is synthesized by a condensation reaction that results
  in the release of H2O (dehydration) and the heterocyclic
  pyrimidine
Further substitution of side chains on the ring produces the
  pharmacologically active barbiturates
Synthesis
Mechanism of Action
Barbiturates potentiate the effect of GABA at the GABA-A receptor. The
GABA-A receptor is a ligand gated ion channel membrane receptor that
allows for the flow of Cl through the membrane in neurons. GABA is the
principle neurotransmitter for this receptor which upon binding causes the
channel to open and creates a negative charge in the transmembrane
potential. This makes it an Inhibitory neurotransmitter


                                         GABA binding site
                                         Barbiturate binding site




                                                                GABA
Mechanism of Action
Barbiturates potentiate the effect of GABA by binding to the GABA-A
receptor at a nearby site and increasing the chloride flow through the
channel. Barbiturates also block the AMPA (2-amino-3-(5-methyl-3-oxo-
1,2- oxazol-4-yl) propanoic acid) receptor which is sensitive to glutamate,
the excitatory neurotransmitter. Glutamate performs the opposite effect
from GABA restricting ion flow and increasing the transmembrane action
potential of the neuron. By blocking this action Barbiturates serve to
increase the duration of the receptor response to GABA and extend the
depressed condition of the cell.
Uses
 Barbiturates have been use in the past to treat a variety of
  symptoms from insomnia and dementia to neonatal jaundice
 They have largely been replaced with drugs such as
  benzodiazepine due to their propensity for addiction and
  reduced effect over the extended use
 Still used widely to treat seizures particularily neonatal
  seizures
 Used when benzo class drugs fail
 Cannot be used for treatment of absence seizures
Structure activity relationship
 Modifying the structure of the hypnotically inactive barbituric acid can
  convert it into a hypnotic barbiturate with physicochemical properties that
  affect its ability to gain access to its sites of action and to interact with its
  receptor.
 Hypnotic activity is introduced into the barbituric acid by the addition of
  side chains, especially if at least one of them is branched, in positions 5.
 Quaternary carbon at position 5 is necessary for activity
 Unsubstituted compound is more acidic than di-substituted
  derivatives and do not depress CNS- unionized drug can penetrate
  the membrane
 Introduction of one alkyl or aryl group at position 5 has little
  effect on acidity, whereas two groups decrease the acidity
 When the sum of C-atoms at position 5 is larger than 7 or 8
  activity drops for example dibenzyl barbituric acid produces no
  effect
 Introduction of a polar functional group such as ether, keto,
  hydroxyl, amino and carboxyl, on the side chain usually destroys
  the depressant effect
contnd
 The length of the side chains in the 5 position influences both the
  potency and the duration of action of the barbituric acid
  derivatives; secobarbital and thiamylal are slightly more potent
  than pentobarbital and thiopental, respectively, because the former
  drugs have slightly longer (three-carbon versus two-carbon) side
  chains in position 5
 Replacing the oxygen atom with a sulfur atom at
  position 2 of an active barbiturate produces a
  barbiturate with a more rapid onset and a shorter
  duration of action; the thiobarbiturates, thiopental
  and thiamylal, have faster onsets and shorter
  durations of action than their oxybarbiturate
  analogues, pentobarbital and secobarbital.
 Methylation of an active barbiturate in position 1
  produces a drug such as methohexital with not
  only a rapid onset and short duration of action
  but also an increased incidence of excitatory side
  effects. Therefore, any chemical modification
  that increases the lipophilicity of a hypnotic
  barbiturate generally increases both its potency
  and its rate of onset while shortening its duration
  of action.
 Many barbiturates have asymmetric carbon atoms in one of the
  side chains attached to carbon 5 of the barbiturate ring. d
  isomers are two times potent, despite their similar access to the
  central nervous system.
 Differences in the potency of stereoisomers suggests interaction
  with the chiral active center of a receptor rather than a
  nonspecific action
Metabolism
 Metabolic transformation of barbiturates influence the duration
  and intensity of their action
 Diethyl barbiturate is excreted unchanged in the urine
 Most of the other barbiturates are metabolized in the liver before
  excretion
 N-methyl barbiturates are demthylated in the liver
 The terminal carbon of the side chain at position 5 is oxidized into
  carboxylic acids
Aldehyde derivative-Paraldehyde
 Aliphatic aldehydes are thought to exert their hypnotic effect by
  being converted into corresponding alcohols
 It is trimer of acetaldehyde and is considered to be cyclic acetal of
  the parent compound
 It is a safe hypnotic and has prompt action
 The main disadvantage is its pungent odour, taste and irritating
  effect on mucosa
Chloral hydrate (trichloroacetaldehyde)
 A crystalline water soluble hydrate
 Its active metabolite is trichloroethanol
 It relieves insomnas without any after effects. However, it causes
  it causes gastric irritation, cardiac and respiratory depression
 Trichloroethanol is excreted in urine as its glucuronide
SAR
 Prolonged use of chloral hydrate leads to a condition similar to
  alcoholism or morphinism.
 To lessen its side effects, some derivatives have been produced
  without side effects. For example trichloroethyl phosphate, which
  is a satisfactory and safe compound
Chloral betaine
 It is an aduct of betaine and carboxymethyl trimethyl
  ammonium
 It is inert, tasteless and odorless compound
 Action similar to chloral hydrate




                           (CH3)3 N+   CH2   CO2-
Petrichloral
 It is a hemi-acetal fromed from chloral hydrate and
  penta erythrol
 Has similar properties to chloral hydrate but free from
  after taste and GI irritation
Alcohols
 Ethyl alcohol
 Is narcotic and depresses, first the highest cerebral center and
  then the lower ones, cerebellum and spinal chord
 Hypnotic activity increases with the increase in molecular
  weight, maximum with n-hexanol or n-octanol, afterwards
  activity declines
 Branching in alkyl chain raises the activity, primary< secondary
  <tertiary
 Chlorination or bromination of simple and branched alcohol
  induces favorabl effect on distribution coefficient. For example
  trichloro or tribromoethanol has strong hypnotic activity
Chlorobutanol
 2 hydroxy, 2 methyl, 1,1,1 trichloropropane (trichloro-2-
  methyl-2-propanol)
 It is a strong hypnotic agent and has been used as
  preanesthetic medication
 It is as dangerous as chloral hydrate
Methyl parafynol
 Has pronounced hypnotic effect with wide margin of
  safety
 Active orally and parenterally
 Short duration of action due to oxidation of triple bond
Ethchlorvynol
 A sedative and hypnotic agent developed by Pfizer in the 1950. It
  was used to treat insomnia, but had largely been superseded
 Still offered where an intolerance or allergy to other drugs exist
 Along with expected sedative effects, ethchlorvynol can cause
  skin rashes, faintness, restlessness and euphoria.
 An overdose is marked by confusion, fever, peripheral numbness
  and weakness, reduced coordination and muscle control, slurred
  speech, and reduced heartbeat.
Synthesis
 By the reaction of lithium acetylide with 1-chloro-1-
  penten-3-one in liquid ammonia
Ethinamate
 is a short-acting carbamate-derivative sedative-hypnotic
  medication used to treat insomnia. Regular use leads to drug
  tolerance, and it is usually not effective for more than 7 days.
  Prolonged use can lead to dependency.
 Synthesized by combining acetylene with cyclohexanone and the
  transformation of the resulting carbinol into carbamate by the
  subsequent reaction with phosgene, and later with ammonia.
Glutarimide derivatives
 Glutarimide is a chemical compound featuring a piperidine ring
  with two ketones attached next to the nitrogen
Glutethimide
 Structurally similar to phenobarbital and produce hypnotic effect
  similar to barbiturates
 Has short duration of action
 Side effects include skin rash, nausea and addiction.
 Administered orally-500mg
1 von 29

Recomendados

Barbiturate von
BarbiturateBarbiturate
BarbiturateRasel Mahbub JNU
27.4K views24 Folien
Benzodiazepines; Diazepam von
Benzodiazepines; DiazepamBenzodiazepines; Diazepam
Benzodiazepines; DiazepamFahad Ullah
44.8K views22 Folien
Sympatholytics von
SympatholyticsSympatholytics
SympatholyticsSadaqat Ali
40.4K views31 Folien
Barbiturates von
BarbituratesBarbiturates
BarbituratesRawalpindi Medical College
32.8K views30 Folien
Antihistamine von
AntihistamineAntihistamine
AntihistamineDHARMENDRA BARIA
63.1K views37 Folien
Narcotics and non narcotics analgesics von
Narcotics and non narcotics analgesicsNarcotics and non narcotics analgesics
Narcotics and non narcotics analgesicsFarazaJaved
127.6K views30 Folien

Más contenido relacionado

Was ist angesagt?

Anticholinergic drugs von
Anticholinergic drugsAnticholinergic drugs
Anticholinergic drugsDrVishal Kandhway
80.8K views26 Folien
parasympathomimetics drugs von
  parasympathomimetics drugs  parasympathomimetics drugs
parasympathomimetics drugsMr. MOHD FAHAD
44.6K views32 Folien
Neuromuscular blocker von
Neuromuscular blockerNeuromuscular blocker
Neuromuscular blockerOmkumar Patel
45.4K views23 Folien
Adrenergic antagonists von
Adrenergic antagonistsAdrenergic antagonists
Adrenergic antagonistskencha swathi
7.4K views28 Folien
Notes sedative & hypnotics von
Notes sedative & hypnoticsNotes sedative & hypnotics
Notes sedative & hypnoticsBabitha Devu
49.2K views36 Folien
Adrenergic drugs. von
Adrenergic drugs.Adrenergic drugs.
Adrenergic drugs.Md kawsar
92.6K views23 Folien

Was ist angesagt?(20)

parasympathomimetics drugs von Mr. MOHD FAHAD
  parasympathomimetics drugs  parasympathomimetics drugs
parasympathomimetics drugs
Mr. MOHD FAHAD44.6K views
Neuromuscular blocker von Omkumar Patel
Neuromuscular blockerNeuromuscular blocker
Neuromuscular blocker
Omkumar Patel45.4K views
Notes sedative & hypnotics von Babitha Devu
Notes sedative & hypnoticsNotes sedative & hypnotics
Notes sedative & hypnotics
Babitha Devu49.2K views
Adrenergic drugs. von Md kawsar
Adrenergic drugs.Adrenergic drugs.
Adrenergic drugs.
Md kawsar92.6K views
Expt 9 Effect of drugs on rabbit eye von Mirza Anwar Baig
Expt 9  Effect of drugs on rabbit eyeExpt 9  Effect of drugs on rabbit eye
Expt 9 Effect of drugs on rabbit eye
Mirza Anwar Baig20.4K views
Skeletal muscle relaxants, Neuromuscular blocking agents, Neuromuscular blockers von Pranav Bansal
Skeletal muscle relaxants, Neuromuscular blocking agents, Neuromuscular blockersSkeletal muscle relaxants, Neuromuscular blocking agents, Neuromuscular blockers
Skeletal muscle relaxants, Neuromuscular blocking agents, Neuromuscular blockers
Pranav Bansal44.3K views
CHOLINERGIC BLOCKERS(CHOLINOLYTICS) von kencha swathi
CHOLINERGIC BLOCKERS(CHOLINOLYTICS)CHOLINERGIC BLOCKERS(CHOLINOLYTICS)
CHOLINERGIC BLOCKERS(CHOLINOLYTICS)
kencha swathi7.9K views

Similar a Barbiturates

Sedative - drm von
Sedative - drmSedative - drm
Sedative - drmDhanashri Mali
429 views50 Folien
Cns sedatives &; hypnotics SAR von
Cns sedatives &; hypnotics SAR Cns sedatives &; hypnotics SAR
Cns sedatives &; hypnotics SAR SURABHI PHARMACY COLLEGE
72 views17 Folien
Sedative Med Chem Lecture von
Sedative Med Chem Lecture Sedative Med Chem Lecture
Sedative Med Chem Lecture sagar joshi
25.7K views99 Folien
Week 6 Alcohol antagonists von
Week 6 Alcohol antagonistsWeek 6 Alcohol antagonists
Week 6 Alcohol antagonistsUbaldo Niña
453 views34 Folien
Barbiturates von
BarbituratesBarbiturates
BarbituratesKhushboo Sharma
31.1K views43 Folien
Sedative and hypnotics von
Sedative and hypnotics Sedative and hypnotics
Sedative and hypnotics HardikAdhyaru3
58 views19 Folien

Similar a Barbiturates(20)

Sedative Med Chem Lecture von sagar joshi
Sedative Med Chem Lecture Sedative Med Chem Lecture
Sedative Med Chem Lecture
sagar joshi25.7K views
Week 6 Alcohol antagonists von Ubaldo Niña
Week 6 Alcohol antagonistsWeek 6 Alcohol antagonists
Week 6 Alcohol antagonists
Ubaldo Niña453 views
Sedative hypnotic drugs /Medicinal Chemistry III(Part Two) von NarminHamaaminHussen
Sedative  hypnotic drugs /Medicinal Chemistry III(Part Two)Sedative  hypnotic drugs /Medicinal Chemistry III(Part Two)
Sedative hypnotic drugs /Medicinal Chemistry III(Part Two)
Sedative hypnotic drugs part I von Domina Petric
Sedative hypnotic drugs part ISedative hypnotic drugs part I
Sedative hypnotic drugs part I
Domina Petric457 views
TERBUTALINE MEDICINAL CHEMISTRY.pptx von Misha Patel
TERBUTALINE MEDICINAL CHEMISTRY.pptxTERBUTALINE MEDICINAL CHEMISTRY.pptx
TERBUTALINE MEDICINAL CHEMISTRY.pptx
Misha Patel471 views
Cholinergic agent von ASHOK GAUTAM
Cholinergic agentCholinergic agent
Cholinergic agent
ASHOK GAUTAM16.6K views
Sedative & Hypnotics ppt von faysalahmed35
Sedative & Hypnotics pptSedative & Hypnotics ppt
Sedative & Hypnotics ppt
faysalahmed3538.8K views

Más de Khalid Hussain

Digestion glycolysis von
Digestion glycolysisDigestion glycolysis
Digestion glycolysisKhalid Hussain
10.8K views37 Folien
Antimalarial drugs: Pyrimidine class (2015) von
Antimalarial drugs: Pyrimidine class (2015)Antimalarial drugs: Pyrimidine class (2015)
Antimalarial drugs: Pyrimidine class (2015)Khalid Hussain
15.9K views10 Folien
TB, historical perspective of anti TB drugs and medicinal chemistry of INH von
TB, historical perspective of anti TB drugs and medicinal chemistry of INHTB, historical perspective of anti TB drugs and medicinal chemistry of INH
TB, historical perspective of anti TB drugs and medicinal chemistry of INHKhalid Hussain
10.1K views17 Folien
Miscellaneous antimalarial agents von
Miscellaneous antimalarial agentsMiscellaneous antimalarial agents
Miscellaneous antimalarial agentsKhalid Hussain
3.9K views13 Folien
Instrumentation 2 von
Instrumentation 2Instrumentation 2
Instrumentation 2Khalid Hussain
4.2K views22 Folien
Instrumentation 1 von
Instrumentation 1Instrumentation 1
Instrumentation 1Khalid Hussain
4.6K views25 Folien

Más de Khalid Hussain(20)

Antimalarial drugs: Pyrimidine class (2015) von Khalid Hussain
Antimalarial drugs: Pyrimidine class (2015)Antimalarial drugs: Pyrimidine class (2015)
Antimalarial drugs: Pyrimidine class (2015)
Khalid Hussain15.9K views
TB, historical perspective of anti TB drugs and medicinal chemistry of INH von Khalid Hussain
TB, historical perspective of anti TB drugs and medicinal chemistry of INHTB, historical perspective of anti TB drugs and medicinal chemistry of INH
TB, historical perspective of anti TB drugs and medicinal chemistry of INH
Khalid Hussain10.1K views
Miscellaneous antimalarial agents von Khalid Hussain
Miscellaneous antimalarial agentsMiscellaneous antimalarial agents
Miscellaneous antimalarial agents
Khalid Hussain3.9K views
Differential scanning calorimetry von Khalid Hussain
Differential scanning calorimetryDifferential scanning calorimetry
Differential scanning calorimetry
Khalid Hussain169.9K views
Theories of chromatography von Khalid Hussain
Theories of chromatographyTheories of chromatography
Theories of chromatography
Khalid Hussain53.6K views

Barbiturates

  • 1. Sedatives and Hypnotics  Sedative: Calm down, treat agitation  Hypnotic: Induce sleep  go to sleep fast, feel fresh when awake  Anxiolytic: Reduce anxiety  physical, emotional, cognitive
  • 3. Barbiturates • Derivatives of Barbituric acid or Malonylurea: Combination of urea and malonic caid • Depressants of the central nervous system, impair or reduce activity of the brain by acting as a Gamma Amino Butyric Acid (GABA) potentiators • Produce alcohol like symptoms such as ataxia (impaired motor control), dizziness and slow breathing and heart rate
  • 4. History • Barbituric acid was first preraed in 1864 by a German scientist - Adolf von Baeyer - by combining urea from animals and malonic acid from apples • Its first derivative utilized as a medicine was used to put dogs to sleep, latter Bayer produced Veronal in 1903 to be used as a sleeping aid • Soon after, phenobarbital and many other barbituric acid derivatives were discovered and marketed Interesting facts • Caused the death of many celebrities such as Jimi Hendrix and Marilyn Monroe • Used by the Nazis during WWII for euthanasia
  • 5. Types Barbituric Acid Amobarbital Phenobarbital Pentobarbital
  • 6. Synthesis Malonic Acid Urea Barbituric Acid Barbituric acid is synthesized by a condensation reaction that results in the release of H2O (dehydration) and the heterocyclic pyrimidine Further substitution of side chains on the ring produces the pharmacologically active barbiturates
  • 8. Mechanism of Action Barbiturates potentiate the effect of GABA at the GABA-A receptor. The GABA-A receptor is a ligand gated ion channel membrane receptor that allows for the flow of Cl through the membrane in neurons. GABA is the principle neurotransmitter for this receptor which upon binding causes the channel to open and creates a negative charge in the transmembrane potential. This makes it an Inhibitory neurotransmitter GABA binding site Barbiturate binding site GABA
  • 9. Mechanism of Action Barbiturates potentiate the effect of GABA by binding to the GABA-A receptor at a nearby site and increasing the chloride flow through the channel. Barbiturates also block the AMPA (2-amino-3-(5-methyl-3-oxo- 1,2- oxazol-4-yl) propanoic acid) receptor which is sensitive to glutamate, the excitatory neurotransmitter. Glutamate performs the opposite effect from GABA restricting ion flow and increasing the transmembrane action potential of the neuron. By blocking this action Barbiturates serve to increase the duration of the receptor response to GABA and extend the depressed condition of the cell.
  • 10. Uses  Barbiturates have been use in the past to treat a variety of symptoms from insomnia and dementia to neonatal jaundice  They have largely been replaced with drugs such as benzodiazepine due to their propensity for addiction and reduced effect over the extended use  Still used widely to treat seizures particularily neonatal seizures  Used when benzo class drugs fail  Cannot be used for treatment of absence seizures
  • 11. Structure activity relationship  Modifying the structure of the hypnotically inactive barbituric acid can convert it into a hypnotic barbiturate with physicochemical properties that affect its ability to gain access to its sites of action and to interact with its receptor.  Hypnotic activity is introduced into the barbituric acid by the addition of side chains, especially if at least one of them is branched, in positions 5.
  • 12.  Quaternary carbon at position 5 is necessary for activity  Unsubstituted compound is more acidic than di-substituted derivatives and do not depress CNS- unionized drug can penetrate the membrane  Introduction of one alkyl or aryl group at position 5 has little effect on acidity, whereas two groups decrease the acidity  When the sum of C-atoms at position 5 is larger than 7 or 8 activity drops for example dibenzyl barbituric acid produces no effect  Introduction of a polar functional group such as ether, keto, hydroxyl, amino and carboxyl, on the side chain usually destroys the depressant effect
  • 13. contnd  The length of the side chains in the 5 position influences both the potency and the duration of action of the barbituric acid derivatives; secobarbital and thiamylal are slightly more potent than pentobarbital and thiopental, respectively, because the former drugs have slightly longer (three-carbon versus two-carbon) side chains in position 5
  • 14.  Replacing the oxygen atom with a sulfur atom at position 2 of an active barbiturate produces a barbiturate with a more rapid onset and a shorter duration of action; the thiobarbiturates, thiopental and thiamylal, have faster onsets and shorter durations of action than their oxybarbiturate analogues, pentobarbital and secobarbital.
  • 15.  Methylation of an active barbiturate in position 1 produces a drug such as methohexital with not only a rapid onset and short duration of action but also an increased incidence of excitatory side effects. Therefore, any chemical modification that increases the lipophilicity of a hypnotic barbiturate generally increases both its potency and its rate of onset while shortening its duration of action.
  • 16.  Many barbiturates have asymmetric carbon atoms in one of the side chains attached to carbon 5 of the barbiturate ring. d isomers are two times potent, despite their similar access to the central nervous system.  Differences in the potency of stereoisomers suggests interaction with the chiral active center of a receptor rather than a nonspecific action
  • 17. Metabolism  Metabolic transformation of barbiturates influence the duration and intensity of their action  Diethyl barbiturate is excreted unchanged in the urine  Most of the other barbiturates are metabolized in the liver before excretion  N-methyl barbiturates are demthylated in the liver  The terminal carbon of the side chain at position 5 is oxidized into carboxylic acids
  • 18. Aldehyde derivative-Paraldehyde  Aliphatic aldehydes are thought to exert their hypnotic effect by being converted into corresponding alcohols  It is trimer of acetaldehyde and is considered to be cyclic acetal of the parent compound  It is a safe hypnotic and has prompt action  The main disadvantage is its pungent odour, taste and irritating effect on mucosa
  • 19. Chloral hydrate (trichloroacetaldehyde)  A crystalline water soluble hydrate  Its active metabolite is trichloroethanol  It relieves insomnas without any after effects. However, it causes it causes gastric irritation, cardiac and respiratory depression  Trichloroethanol is excreted in urine as its glucuronide
  • 20. SAR  Prolonged use of chloral hydrate leads to a condition similar to alcoholism or morphinism.  To lessen its side effects, some derivatives have been produced without side effects. For example trichloroethyl phosphate, which is a satisfactory and safe compound
  • 21. Chloral betaine  It is an aduct of betaine and carboxymethyl trimethyl ammonium  It is inert, tasteless and odorless compound  Action similar to chloral hydrate (CH3)3 N+ CH2 CO2-
  • 22. Petrichloral  It is a hemi-acetal fromed from chloral hydrate and penta erythrol  Has similar properties to chloral hydrate but free from after taste and GI irritation
  • 23. Alcohols  Ethyl alcohol  Is narcotic and depresses, first the highest cerebral center and then the lower ones, cerebellum and spinal chord  Hypnotic activity increases with the increase in molecular weight, maximum with n-hexanol or n-octanol, afterwards activity declines  Branching in alkyl chain raises the activity, primary< secondary <tertiary  Chlorination or bromination of simple and branched alcohol induces favorabl effect on distribution coefficient. For example trichloro or tribromoethanol has strong hypnotic activity
  • 24. Chlorobutanol  2 hydroxy, 2 methyl, 1,1,1 trichloropropane (trichloro-2- methyl-2-propanol)  It is a strong hypnotic agent and has been used as preanesthetic medication  It is as dangerous as chloral hydrate
  • 25. Methyl parafynol  Has pronounced hypnotic effect with wide margin of safety  Active orally and parenterally  Short duration of action due to oxidation of triple bond
  • 26. Ethchlorvynol  A sedative and hypnotic agent developed by Pfizer in the 1950. It was used to treat insomnia, but had largely been superseded  Still offered where an intolerance or allergy to other drugs exist  Along with expected sedative effects, ethchlorvynol can cause skin rashes, faintness, restlessness and euphoria.  An overdose is marked by confusion, fever, peripheral numbness and weakness, reduced coordination and muscle control, slurred speech, and reduced heartbeat.
  • 27. Synthesis  By the reaction of lithium acetylide with 1-chloro-1- penten-3-one in liquid ammonia
  • 28. Ethinamate  is a short-acting carbamate-derivative sedative-hypnotic medication used to treat insomnia. Regular use leads to drug tolerance, and it is usually not effective for more than 7 days. Prolonged use can lead to dependency.  Synthesized by combining acetylene with cyclohexanone and the transformation of the resulting carbinol into carbamate by the subsequent reaction with phosgene, and later with ammonia.
  • 29. Glutarimide derivatives  Glutarimide is a chemical compound featuring a piperidine ring with two ketones attached next to the nitrogen Glutethimide  Structurally similar to phenobarbital and produce hypnotic effect similar to barbiturates  Has short duration of action  Side effects include skin rash, nausea and addiction.  Administered orally-500mg