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Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

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Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

Dr. yturtodka Atsitareift e-Libran/CHAPTER 12Central Nervous System DepressantsSHENGQUAN LIUCHAPTER OVERVIEWAlthough the brain is undoubtedly the most

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2t wondrously complex organ, it is possible to distil the way it works into two opposing forces; excitation and inhibition (depressing). Central nervou

s system (CNS) depressants are drugs that can be used to slow down or "depress" the functions of the CNS. Although many agents have the capacity to de Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

press the function of the CNS, CNS depressants discussed in this chapter include only anxiolytics, sedative-hypnotics, and antipsychotics.There is som

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

e overlap between the first two groups. They often have several structural features in common and likewise often share al least one mode of action, po

Dr. yturtodka Atsitareift e-Libran/CHAPTER 12Central Nervous System DepressantsSHENGQUAN LIUCHAPTER OVERVIEWAlthough the brain is undoubtedly the most

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2ort one—benzodiazepines. Z-drugs. barbiturates, and a miscellaneous group.Antipsychotic drugs—previously known as neuroleptic drugs. antischi&phrenic

drugs, or major tranquilizers—arc used in the symptomatic treatment of thought disorders (psychoses). most notably the schizophrenias. Antipsychotics Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

are grouped into typical and atypical categories. Both categories share a common feature, a dopamine (DA)-like structure, often hydrophohically substi

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

tuted. This feature can be related to the most commonly cited action of these agents, competitive antagonism of DA at Ds or occasionally Di or Da rece

Dr. yturtodka Atsitareift e-Libran/CHAPTER 12Central Nervous System DepressantsSHENGQUAN LIUCHAPTER OVERVIEWAlthough the brain is undoubtedly the most

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2 produce extrapyramidal symptoms (EPS), because they are less able to block striata D> receptors vis-à-vis limbic D; and Di receptors, and (b> more ac

tive against negative symptoms (social withdrawal, apathy, anhedonia).o anxiolytic, SEDATIVE, ANDHYPNOTIC AGENTSIn addition to benzodiazepines, barbit Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

urates, and a miscellaneous group, many drugs belonging to other pharmacological classes may possess one or more of the anxiolytic, sedative, and hypn

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

otic activities. An arbitrary classification of these agents is as follows:I.GABAạ receptor modulators• Benzodiazepines arc highly effective anxiolyti

Dr. yturtodka Atsitareift e-Libran/CHAPTER 12Central Nervous System DepressantsSHENGQUAN LIUCHAPTER OVERVIEWAlthough the brain is undoubtedly the most

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2azolam, ami quazepam). They bind to benzodiazepine-binding sites on GABAạ receptor (also known as benzodiazepine receptor |BzR|). They are sometimes c

alled benzodiazepine receptor agonists (BzRAs).•Nonbcnzodiazcpinc hypnotics (Z-drugs): Imidazopyri-dine (zolpidem), pyrazolopyrimidine (zaleplon), and Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

cyclopyrrolone (zopiclone and its |5|-| + ]-enantiomer cszopiclonc).•Barbiturates including amobarbital, aprobarbital, butabarbital, pentobarbital, p

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

henobarbital, and secobarbital are largely obsolete and superseded by benzodiazepines. Their use is now confined to anesthesia and treatment of epilep

Dr. yturtodka Atsitareift e-Libran/CHAPTER 12Central Nervous System DepressantsSHENGQUAN LIUCHAPTER OVERVIEWAlthough the brain is undoubtedly the most

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2 Administration (FDA)-approvcd drugs for insomnia include nine BzRAs (five benzodiazepines, four non-bcnzodiazcpincs) and ramcltcon.3Atypical azaspiro

decanediones: Buspirone is a partial 5-HT|A receptor agonist and an anxiolytic. Il is less sedative and has less abuse potential.4Miscellaneous drugs Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

such as chloral hydrate, meprobamate, and glutethimide are no longer recommended, but occasionally used.5Antipsychotics and anticonvulsants. It has be

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

en proposed that DA has a facilitative and active role in the sleep-wakefulness cycle. Waking appears to be a state maintained by Di receptor activati

Dr. yturtodka Atsitareift e-Libran/CHAPTER 12Central Nervous System DepressantsSHENGQUAN LIUCHAPTER OVERVIEWAlthough the brain is undoubtedly the most

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2tazapine have been shown to be effective in the treatment of insomnia in patients with depression. Several selective serotonin reuptake inhibitors (SS

RIs), including escitalopram. fluoxetine, flu-voxaminc. paroxetine, ami sertraline, became the first-line therapy for some anxiety disorders in 1990s Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

because they are not as addictive as benzodiazepines.7Sedative HI-antihistamines: diphenhydramine and doxyl-ainine:Diphenhydramine is sometimes used a

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

s sleeping pills, particularly for wakeful children. It is proposed that histamine may have an involvement in wakefulness and rapid eye movement (REM)

Dr. yturtodka Atsitareift e-Libran/CHAPTER 12Central Nervous System DepressantsSHENGQUAN LIUCHAPTER OVERVIEWAlthough the brain is undoubtedly the most

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2a presynaptic autoreceptor regulating the443Dr. Murtữdhn Alfharetft f-Libraiy444 II7/.WW and Cisvold's Textbook of Organic Medicinal and Pharmaceutica

l Chemistrysynthesis and release of histamine. The HI receptor agonists and the Hi receptor antagonists increase wakefulness, whereas the Hl receptor Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

antagonists and H-. receptor agonists have the opposite effect. Another example of HI -antihistamines is doxylamine.80-Adrenoceptor antagonists (e.g.,

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

propranolol) are sometimes used by actors and musicians to reduce the symptoms of stage fright, but their use by snooker players to minimize tremor i

Dr. yturtodka Atsitareift e-Libran/CHAPTER 12Central Nervous System DepressantsSHENGQUAN LIUCHAPTER OVERVIEWAlthough the brain is undoubtedly the most

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2leep-producing agent).•Linoleamide and 9,IO-octadecenoamidc arc possible endogenous sleep-producing agents and arc positive modulators of GABAa recept

ors.2•Anandamide is an endogenous cannabinoid that might be used as a lead to search for new hypnotics.The properties and side effects of FDA-approved Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

hypnotics and commonly used but not FDA-approved hypnotics arc reviewed.’'4 Older sedative-hypnotic drugs depress the CNS in a dose-dependent manner,

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

progressively producing calming or drowsiness (sedation), sleep, unconsciousness, surgical anesthesia, coma, and eventually death from respiratory an

Dr. yturtodka Atsitareift e-Libran/CHAPTER 12Central Nervous System DepressantsSHENGQUAN LIUCHAPTER OVERVIEWAlthough the brain is undoubtedly the most

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2onionized form at physiological pH. their high lipophilicity is an important factor for following properties, (a) Most of them are absorbed well from

the gastrointestinal (Gl) tract, with good distribution to the brain. This property is responsible for the rapid onset of CNS effects of triazolam, th Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

iopental, and newer hypnotics. (b) Many sedative-hypnotics cross the placental barrier during pregnancy, (c) They are also detectable in breast milk,

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

(d) Some drugs with highest lipophilicity have short duration of action because of their redistribution, (e) Most drugs in this class are highly prote

Dr. yturtodka Atsitareift e-Libran/CHAPTER 12Central Nervous System DepressantsSHENGQUAN LIUCHAPTER OVERVIEWAlthough the brain is undoubtedly the most

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2e benzodiazepines is metabolism, and most of them are extensively metabolized. Consequently, their duration of action depends mainly on the rate of me

tabolism and if their metabolites are active. Benzodiazepines are the most important drugs in both groups; therefore, the two groups arc discussed tog Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

ether in the first section.CABAa Receptors, Benzodiazepines, and Related CompoundsGABA system (deficiency of GABA activity in CNS) is important in the

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

pathophysiology of anxiety and insomnia. GABA IS the most common and major inhibitory neurotransmitter (NT) in the brain and it exerts its rapid inhi

Dr. yturtodka Atsitareift e-Libran/CHAPTER 12Central Nervous System DepressantsSHENGQUAN LIUCHAPTER OVERVIEWAlthough the brain is undoubtedly the most

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2ropic GABAu receptor. GABAa receptor is the target for many anxiolytics and sedative-hypnotic agents including benzodiazepines. barbiturates, zolpidem

, zaleplon, eszopiclone. steroids, anticonvulsive agents, and many other drugs that bind to different binding sites of the GABAa receptors in neuronal Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

membranes in the CNS.5f’ It is a ligand-gated chloride ion channel. Upon activation. Cl influx is increased and the membrane becomes hypcrpolarizcd.

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

resulting in neuronal inhibition.GABAa receptor exists as heteropentomeric transmembrane subunits arranged around a central chloride ion (Cl ) channel

Dr. yturtodka Atsitareift e-Libran/CHAPTER 12Central Nervous System DepressantsSHENGQUAN LIUCHAPTER OVERVIEWAlthough the brain is undoubtedly the most

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2together make up the structure of GABAa receptors come from the subunit families cr. (3. y, 8, e, IT, p, and ị. There are six isoforms of the a-polypc

ptide (a|-CTf,). four of the ịi with two splice variants, and three of the y with two variants. .Most receptors consist of a, fi. and y combinations. Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

Of these. tt|, /?2. and y> are most common. The most common pcntomcric GABA receptor combination includes two subunit. Other

Ebook Textbook of organic medicinal and pharmaceutical chemistry (12 edition): Part 2

highly expressed combinations are «2-

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