Applications anticonvulsant agents

New more effective anticonvulsants are neededfor autoinjector applications. Anticonvulsants that are water soluble and effective in halting nerve agent-induced seizure activity as well as preventing recurrence of the seizure activity will improve the recovery of seriously poisoned casualties. 

Applications are mainly focused on the determination of drugs (e.g., anticonvulsant agents, barbiturates, (3-blockers, diuretics, corticoids, stimulants) in formulations of physiological fluids, such as serum, plasma, or urine. In this case, the direct injection capability of MLC is especially appreciated. Simple filtration of the sample permits the direct injection of the physiological fluids in the chromatographic system, with no noticeable damage after repetitive injections. MLC has also been extended to the analysis of samples of industrial, environmental, veterinarian, and nutritional interest. 

Major Applications Electroluminescent devices, semiconductor wafer, corrosion inhibitors, antibacterial agent,i anticonvulsant agent, anticancer agent o Safety/Toxicity No data available... 

Other applications include bioequivalent measurements of bromazepam, an anticonvulsant, in human plasma. The lower limit of quantitation (LLOQ) was 1 ng/mL (Gongalves et al. 2005). Kuhlenbeck et al. (2005) studied antitussive agents (dextromethorphan, dextrophan, and guaifenesin) in human plasma LLOQ values were 0.05, 0.05, and 5 ng/mL, respectively. Other compounds studied were nucleoside reverse transcriptase inhibitors, zidovudine (AZT) and lamivudine (3TC) (de Cassia et al. 2004) and stavudine (Raices et al. 2003) in human plasma, and paclitaxel, an anticancer agent, in human serum (Schellen et al. 2000). 

The antianxiety effects of chlordiazepoxide (165) were described in 1960 and this compound was followed by diazepam (135). These two drugs have captured 75% of the market for sedatives in the USA. Other benzodiazepines used as antianxiety agents include oxazepam (166 R = H), a metabolite of diazepam that is better tolerated, lorazepam (166 R = Cl) and potassium clorazepate (167). Prazepam is the iV-cyclopropylmethyl analogue of diazepam. The benzodiazepines have other therapeutic applications, many being used for inducing sleep, diazepam and nitrazepam are anticonvulsants and flurazepam (168) is both an antianxiety agent and a potent hypnotic. Thieno- and pyrazolo-1,4-diazepinones isosteric with diazepam have similar pharmacological properties (B-81 Ml 10604). 

Some of these agents appear to have a very selective action at Hs-receptors, though there is some cross-talk with 5-HT3 receptors. None of these agents are used therapeutically yet, but suggested applications include inhibition of neurogenic microvascular leakage in airways, prevention of myocardial ischaemia, as anticonvulsants, appetite suppressants and cognition enhancers. 

Benzodiazepines are an important class of pharmacologically active compounds finding application as anticonvulsant, antianxiety, and hypnotic agents. Benzodiazepine derivatives also find commercial use as dyes for acrylic fibers and as anti-inflammatory agents. Jarikote and coworkers have developed a new and efficient method for the regioselective synthesis of 1,5-benzodiazepines in excellent isolated yields in short reaction times nsing a room-temperature ionic liquid, namely,... 

Convulsive Antidote Nerve Agent (CANA) is a convulsion antidote for nerve agents. CANA is an auto-injector that contains 2ml of diazepam (more commonly known as Valium) as the anticonvulsant. Diazepam is fully approved for this application by the USFDA. It is used only as buddy-aid, never self injected. CANA is a note Q item requiring vault or safe storage. Additionally, this item must be stored at a controlled room temperature of 59-86 degrees Fahrenheit. The shelf life is two years. 

The anticonvulsant activity of 39 in an actual disease state, as well as its toxic side-effects, were assessed in a controlled trial conducted on 24 epileptic dogs76. The results indicated that 39 is an efficient antiepileptic agent there was a mean reduction of 61% in seizure frequency in 15 epileptic dogs treated orally with 39 when compared with their pretreatment frequency. However, this trial also indicated that toxic side-effects would prevent a practical application as a therapeutic agent in medicine. Liver disease was noted in 3 of 15, pancreatic disease in 2 of 15, and there was some indication that bone-marrow suppression and cardiomyopathy may be associated with exposure to 39. 

Benzodiazepines are often bioactive compounds, widely used as anticonvulsants, antianxiety, hypnotic agents, analgesics, antidepressives, and anti-inflammatory drugs (Figure 19) [159]. For instance, 1,5-benzodiazepines are useful precursors for the synthesis of some benzodiazepine derivatives with pharmacological properties, such as tri-axolo-, triazolo-, oxadiazolo-, oxazino-, or furano-benzodiazepines. In particular, the application of these compoxmds has been also extended to various diseases, such as cancer, viral infection, and cardiovascular disorders. 

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