Sedative activity

Adouetine-Z was reported to possess discrete central sedative activity possibly of central sympatholytic origin 154). 

Frangufoline showed strong sedative activity at a dose of 3 mg/kg (the effect was monitored by measuring the prolongation of hexobarbi-tal-induced sleeping time of mice). Additivity was observed between frangufoline and nuciferine, the latter an aporphine alkaloid also 

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According to Nyman the pharmacological action of hyoscine is considerably modified in the quaternary compounds of the alkaloid, e.g., the inhibiting action on salivary secretion is greatly increased in the methonitrate, as is also the spasmolytic activity, but the mydriatic action is unchanged and the central sedative activity disappears. 

T. Kimura, M. Miki, K. Watanabe, S. Kondo, I. K. Ho, I. Yamamoto, Metabolism of a Novel Hypnotic, /VLphcnacy I uridine, and Hypnotic and Sedative Activities of Its Enantiomer Metabolites in Mouse , Xenobiotica 2000, 30, 643 - 653. 

Several other cyclic imidic compounds containing a piperidine-2,6-dione skeleton (glutethimide, pyrido- and amino-glutethimide, thalidomide) and having similar hypnotic-sedative activity as barbiturates were resolved on a vancomycin CSP [7,157],... 

A well known example of tragic consequences is provided by "Thalidomide" (or "Contergan") which was commercialised in the 60 s whereas the (/ )-enantiomer shows a weak sedative activity, the enantiomer of (5)-configuration, administered together in the racemate, caused in the expectant mothers a teratogenic effect (malformations) on the foetus. 

Hypnotics fall into different categories, including the benzodiazepines (e.g., triazolam, temazepam, clotiaze-pam, nitrazepam), barbiturates (e.g., hexobarbital, pentobarbital), chloral hydrate, and Hi-antihistamines with sedative activity (p. 114). Benzodiazepines act at specific receptors (p. 226). The site and mechanism of action of barbiturates, antihistamines, and chloral hydrate are incompletely understood. 

In normal subjects the tricyclics only show anticholinergic and sedative activity but have no mood elevating action. In depressed subjects their mood elevating effect has a delay of 2-3 weeks. The reasons for this delay are unknown and could be both pharmacokinetic or pharmacodynamic in natme. 

Its adverse reactions such as fatigue, drowsiness and ataxia are mainly related to its sedative activity. Some tolerance can occur for these effects. 

B. Since GABA is an inhibitory neurotransmitter, agents that potentiate its action are likely to be CNS depressants with sedative activity. GABA has no significant effect on blood pressure and will decrease the incidence of seizures. It has no direct ability to relieve pain. 

A. Diazepam is metabolized in the liver by CYP3A4 and CYP2C19 efavirenz inhibits both of these isozymes and is likely to increase plasma levels of diazepam. Diazepam is almost completely converted to inactive metabolites therefore, renal elimination is not much of a concern. Lamivudine may produce fatigue as a side effect but does not potentiate the depressant activity of diazepam. Zidovudine does not induce cytochrome P450 activity, and diazepam does not have to be converted to an active form for sedative activity. 

Zolpidem. Zolpidem is an imidazolopyridine that, like CL 218,872, binds with high affinity to aip2Y2 receptors. In contrast to CL 218,872, zolpidem differentiates within benzodiazepine type 11 receptors in that it displays a 20-fold reduced affinity at 02 2 2 rid otjpjyj receptors, but shows nearly no affinity to 0C5P2y2 receptors (Pritchett and Seeburg 1990). Zolpidem is also unusual in that it has sedative activity at lower doses than those producing anxiolytic, muscle relaxant, and anticonvulsant effects and is consequently marketed for night sedation. 

Glutethimide has strong sedative activity and is an inducer of the liver microsomal enzymes. 

Both geometrical isomers of 173 were isolated. Similar reactions in the quinoline and isoquinoline series gave 174 and 175, respectively. Some of these products exhibited hypnotic and sedative activity. 

Some derivatives 14 showed marked sedative activity comparable or superior to that exhibited by diazepam (73FES494 80FES279). 

Similarly, the synthesis of 8,9-dihydropyrrolo[2,l-c/][l,5]benzothiazep-ine-7,10(6//,7u//)-dione 5,5-dioxides (16) was carried out by cyclizing l-(2-benzylsulfonylphenyl)pyrrolidin-5-one-2-carboxylates (15) in boiling xylene in the presence of potassium (Scheme 7) (72FES1003 73FES494). 7u-Carboxyethyl-8-methyl derivative 16 showed slight sedative activity (73FES494). 

FES765). Compound 30 showed sedative activity similar to that of diazepam. 

The structure-activity relationship is also demonstrated by an alternative experiment. Since the sedative property of a drug requires that the drug be transported directly to the nervous system, a decrease in hydrophobic bonding should result in an increase in sedative activity. The successive introduction of methyl groups to adamantane carboxamide (110) does result in a progressive increase in the sedative activity of the drug in mice 249 ... 

CRITICAL ASSESSMENT OF THE METHOD Locomotion tests estimate whether a test substance possesses psychostimulant or sedative activity, but... 

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