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The Development of diazepam as an anxiolytic - Essay Example

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Leo Sternbach a worker at Hoffmann-La Roche synthesized benzodiazepine, chlordiazepoxide (Librium) in 1955 while working for the formulation of tranquilizers. In the initial stages the pharmacological properties of the compounds were unsatisfactory and the project was stopped by…
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The Development of diazepam as an anxiolytic
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The Development of diazepam as an anxiolytic

Download file to see previous pages... Later, diazepam was marketed in 1963 by Hoffmann–La Roche under the trade name Valium. Thus two drugs emerged as the most successful commercially available drugs revolutionizing the science of anti-anxiolytic drugs. By the year 1970s they potentially replaced older drugs for sedative and hypnotic uses (Shorter, 2005).
Diazepam belongs to benzodiazepine group. Diazepam acts on ascending reticular formation (responsible for wakefulness) in midbrain and on limbic system (responsible for thought). Muscle relaxation is produced by primary medullary site of action and ataxia is due to action on cerebellum (Tripathi, 2008; Rang & Dale, 2007; Brunton, 2005).
Diazepam binds to benzodiazepine binding site on GABAA receptor Cl- channel complex. GABAA receptor is a pentameric structure (like a lily flower). It contains many sub-units and encloses Cl- channel. The opening of Cl- channel is modulated by GABA.
Diazepam by binding to benzodiazepine binding site (α/γ subunit interface) facilitates GABA action (more amount of GABA will bind to GABAA receptor). It is not a GABA mimetic, it only facilitates GABA mediated Cl- channel opening. Opening of Cl- channel causes influx of Cl- ions and causes hyperpolarization. This decreases the firing rate of neurons. Therefore it possesses hypnotic action- induction of sleep- reticular activating system- depresses CNS- decreases the spread of epileptic discharge, therefore possesses anticonvulsant action (Tripathi, 2008; Rang & Dale, 2007; Brunton, 2005).
The chloride channel is gated by the primary ligand GABA acting on GABAA receptor located on the β- subunit. The benzodiazepine (BZD) receptor located on the interface of α and γ subunits modulates GABAA receptor in either direction (Tripathi, 2008).
Oral absorption of Diazepam is good. Diazepam is widely distributed in body; absorption from intramuscular site of administration is ...Download file to see next pagesRead More
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