Structures of drugs affecting the CNS and their SAR

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Structures of drugs affecting the CNS and their SAR
Ayman Barghout
Fichas por Ayman Barghout, actualizado hace más de 1 año
Ayman Barghout
Creado por Ayman Barghout hace más de 8 años
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Barbituric acid
General structure of barbiturates
Uses of barbiturates They were popular in treating insomnia, now they are not usually used due to their higher toxicity, tolerance, and dependance. They have sedative, hypnotic and anxiolytic action
Mechanism of action of barbiturates and BZs (Potentiating the action of GABA) Enhancing the ability of GABA to bind to the GABA-A receptor which alters its conformation and as a result GABA can bind more easily (allosteric regulation)
Thiopental Ultra-short acting barbiturate Available as Sodium salt for IV Induction of anesthesia immediate onset (~ 35 secs), very short duration of action (~ 7.5 mins) Rapid redistribution and metabolism
Methohexital ltra short acting barbiturate for the induction of anesthesia Outpatient oral surgical procedures cuz: Quick onset Rapid recovery
Secobarbital Short acting barbiturate relatively potent with rapid onset of action 10-15 mins Short duration 3-4 hours
Amobarbital Intermediate acting barbiturate slow onset (30 - 60 mins) intermediate duration (6 - 8 hours)
Phenobarbital Long acting barbiturate slow onset ( 45 - 60 minutes ) Long duration ( 10 - 16 hours ) Typical anti-convulsant
General structures of benzodiazepines
Diazepam Long acting anxiolytic, short term management of insomnia associated with daytime anxiety Rapid control of status epilepticus
Flurazepam Higher lipid soluble and more potent than diazepam. Metabolised by N-dealkylation and hydroxylation gives active metabolites
Oxazepam Short acting anxiolytics for short term management of insomnia preferred with patients with hepatic impairment, but with withdrawal symptoms.
Lorazepam Same as Oxazepam but more potent due to the 2-Cl.. Effective when given IV for rapid control of status epilepticus
Clorazepic acid Clorazepate is an intermediate acting anxiolytic prodrug, (Oral) decarboxylated to Nordiazepam then hydroxylated to Oxazepam. Treatment of epilepsy and to relief anxiety associated with alcohol withdrawal.
Clonazepam Mainly metabolized through nitro reduction. Approved by FDA for treatment of epilepsy and panic disorder.
Midazolam Imidazobenzodiazepine derivative Fast onset and short duration ( 3 - 4 hours) Preoperative secation and induction of general anesthesia.
Alprazolam Triazolobenzodiazepine derivative. Short acting anxiolytic ( 10 - 15 hours) Approved for management of anxiety disorder
Quazepam Increased selectivity due to sulfur substitution. Long acting due to N1 Substitutions, Cl & F.
Phenytoin Hydantoin derivative ring contracted analogue of phenobarbital All kind of seizure except for absence seizure. Inhibits the excessive neuronal firing by binding to a site neigboring to VGSC.
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