Diazepam profiles

FIGURE 1.48 (A) Averaged diazepam profiles from pharmacokinetic studies. (B) Diazepam profile for one study with one dog, both catheters cephalic. (C) Averaged nordiazepam profiles from pharmacokinetic studies. (D) Averaged oxazepam profiles from pharmacokinetic studies.168 (Reproduced with permission from the American Chemical Society and the authors.)... 

N. Inotsume, J. Fujii, M. Nakano, Plasma Concentration Profile of Diazepam After Oral Administration of the Open-Ring Form of Diazepam to Man , Chem. Pharm. Bull. 1986, 34, 937 - 940. 

During the early twentieth century the barbiturates were used in children and adolescents for their sedative and hypnotic effects however, their safety profile and propensity to cause physical dependence led scientists in search of safer anxiolytics. The development of animal models of behavioral disorders facilitated the formulation of drugs with more specific central nervous system (CNS) effects. In 1959, chlordiazepoxide (Librium) was the first benzodiazepine (BZ) to receive a patent. It entered the market in 1960, followed by diazepam (Valium) in 1963. Today, over 35 BZs have been formulated and over 10 are available in the United States (Ballenger, 1995 Hobbs et ah, 1996). 

Wahlestedt C, Pich EM, Koob GF, et al Modulation of anxiety and neuropeptide Y-Yl receptors by antisense oligodeoxynucleotides. Science 259 528-531, 1993 Waka T, Fukada N Pharmacologic profile of a new anxiolytic, DN 2327 effect of R015-1788 and interaction with diazepam in rodents. Psychopharmacology 103 314-322, 1991... 

The pharmacokinetic profile is different with different compounds. Diazepam after oral administration is completely and rapidly absorbed from the proximal small intestine. Oxazepam is least rapidly absorbed while lorazepam is an intermediately absorbed between these two. They are metabolised in liver by dealkylation and hydroxylation and excreted in urine as glu-curonide conjugates. They cross the placental barrier and are secreted in milk. 

Kelly, T.H. et al., Performance-based testing for drugs of abuse dose and time profiles of marijuana, amphetamine, alcohol, and diazepam, J. Anal. Toxicol., 17, 264, 1993. 

Adverse Effects. The most common side effects associated with tizanidine include sedation, dizziness, and dry mouth.40 As indicated, however, tizanidine tends to have a more favorable side effect profile than other alpha-2 agonists, and this drug produces less generalized weakness than oral baclofen or diazepam. Tizanidine may therefore be a better alternative to these other agents in patients who need to reduce spasticity while maintaining adequate muscle strength for ambulation, transfers, and so forth. 

Benzodiazepines that are structurally related to diazepam and that have qualitatively similar pharmacological profiles (e.g anxiolytic, anticonvulsant, muscle relaxant and sedative). 

Fig. 16. Effects of diazepam on the power spectrum of the quantified EEG. Diazepam dose-dependently decreases power in die lower frequency range, with an inversion of this effect at high frequencies. The decreases in power are more marked in die hippocampus, whereas the increases are more marked in the cortex. Similar profiles are observed with other benzodiazepines and benzodiazepine-like substances such as zolpidem (data not shown).

Pharmacokinetic and pharmacodynamic profiles of olanzapine have been extensively reviewed (266). Olanzapine does not inhibit CYP isozymes, and no clinically significant metabolic interactions were found of olanzapine with aminophylline, biperiden, diazepam, ethanol, fluoxetine, imipramine, lithium, or R/S-warfarin. 

SAFETY PROFILE Poison by ingestion and intraperitoneal routes. Moderately toxic by subcutaneous route. Human systemic effects by ingestion wakefulness, withdrawal, nausea and vomiting. An experimental teratogen. Other experimental reproductive effects. A tranquilizer. When heated to decomposition it emits very toxic fumes of NOx and Cl". See also DIAZEPAM. 

HBS Hydrodynamically balanced system. A CR oral dosage form (capsule or tablet), which is designed to prolong the residence time within the stomach. Increased time for dissolution, prolonged absorption phase, and improved pharmacokinetic profile. Madopar HBS or Prolopa HBS (L-dopa + Benserazide) Vahelease (diazepam). 

Hydroxybenzodiazepines represent active metabolites of many clinically useful benzodiazepines (e.g., diazepam), and consequently a large number of 3-substituted derivatives have been prepared and evaluated as anxiolytics in their own right. These compounds often show comparable potency to that of the parent benzodiazepines, but have a dramatically different metabolic profile. In hu-... 

Pyrazoloquinolines frequently possess subnanomolar affinity for the BZR, but show no subtype selectivity in their binding (396). Unlike the benzodiazepines,some pyrazoloquinolines also bind to the diazepam-insensitive receptor subtypes (a4 and 0 6). Although several compounds show partial agonist and anxio-selective profiles (e.g., C(jS9896) in preclinical models, there is no evidence to suggest any... 

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