Simplified molecular-input line-entry system
The simplified molecular-input line-entry system is a specification in the form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules; the original SMILES specification was initiated in the 1980s. It has since been extended. In 2007, an open standard called. Other linear notations include the Wiswesser line notation, ROSDAL, SYBYL Line Notation; the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. Acknowledged for their parts in the early development were "Gilman Veith and Rose Russo and Albert Leo and Corwin Hansch for supporting the work, Arthur Weininger and Jeremy Scofield for assistance in programming the system." The Environmental Protection Agency funded the initial project to develop SMILES. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems.
In 2007, an open standard called "OpenSMILES" was developed by the Blue Obelisk open-source chemistry community. Other'linear' notations include the Wiswesser Line Notation, ROSDAL and SLN. In July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is considered to have the advantage of being more human-readable than InChI; the term SMILES refers to a line notation for encoding molecular structures and specific instances should be called SMILES strings. However, the term SMILES is commonly used to refer to both a single SMILES string and a number of SMILES strings; the terms "canonical" and "isomeric" can lead to some confusion when applied to SMILES. The terms are not mutually exclusive. A number of valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol. Algorithms have been developed to generate the same SMILES string for a given molecule; this SMILES is unique for each structure, although dependent on the canonicalization algorithm used to generate it, is termed the canonical SMILES.
These algorithms first convert the SMILES to an internal representation of the molecular structure. Various algorithms for generating canonical SMILES have been developed and include those by Daylight Chemical Information Systems, OpenEye Scientific Software, MEDIT, Chemical Computing Group, MolSoft LLC, the Chemistry Development Kit. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database; the original paper that described the CANGEN algorithm claimed to generate unique SMILES strings for graphs representing molecules, but the algorithm fails for a number of simple cases and cannot be considered a correct method for representing a graph canonically. There is no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, double bond geometry; these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES.
A notable feature of these rules is. The term isomeric SMILES is applied to SMILES in which isotopes are specified. In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph; the chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree; the resultant SMILES form depends on the choices: of the bonds chosen to break cycles, of the starting atom used for the depth-first traversal, of the order in which branches are listed when encountered. Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as for gold. Brackets may be omitted in the common case of atoms which: are in the "organic subset" of B, C, N, O, P, S, F, Cl, Br, or I, have no formal charge, have the number of hydrogens attached implied by the SMILES valence model, are the normal isotopes, are not chiral centers.
All other elements must be enclosed in brackets, have charges and hydrogens shown explicitly. For instance, the SMILES for water may be written as either O or. Hydrogen may be written as a separate atom; when brackets are used, the symbol H is added if the atom in brackets is bonded to one or more hydrogen, followed by the number of hydrogen atoms if greater than 1 by the sign + for a positive charge or by - for a negative charge. For example, for ammonium. If there is more than one charge, it is written as digit.
Regulation of therapeutic goods
The regulation of therapeutic goods, drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the national level by a single agency. In other jurisdictions they are regulated at the state level, or at both state and national levels by various bodies, as is the case in Australia; the role of therapeutic goods regulation is designed to protect the health and safety of the population. Regulation is aimed at ensuring the safety and efficacy of the therapeutic goods which are covered under the scope of the regulation. In most jurisdictions, therapeutic goods must be registered. There is some degree of restriction of the availability of certain therapeutic goods depending on their risk to consumers. Modern drug regulation has historical roots in the response to the proliferation of universal antidotes which appeared in the wake of Mithridates' death. Mithridates had brought together physicians and shamans to concoct a potion that would make him immune to poisons.
Following his death, the Romans became keen on further developing the Mithridates potion's recipe. Mithridatium re-entered western society through multiple means; the first was through the Leechbook of the Bald, written somewhere between 900 and 950, which contained a formula for various remedies, including for a theriac. Additionally, theriac became a commercial good traded throughout Europe based on the works of Greek and Roman physicians; the resulting proliferation of various recipes needed to be curtailed in order to ensure that people were not passing off fake antidotes, which led to the development of government involvement and regulation. Additionally, the creation of these concoctions took on ritualistic form and were created in public and the process was observed and recorded, it was believed that if the concoction proved unsuccessful, it was due to the apothecaries’ process of making them and they could be held accountable because of the public nature of the creation. In the 9th century, many Muslim countries established an office of the hisba, which in addition to regulating compliance to Islamic principles and values took on the role of regulating other aspects of social and economic life, including the regulation of medicines.
Inspectors were appointed to employ oversight on those who were involved in the process of medicine creation and were given a lot of leigh weigh to ensure compliance and punishments were stringent. The first official'act', the'Apothecary Wares and Stuffs' Act was passed in 1540 by Henry VIII and set the foundation for others. Through this act, he encouraged physicians in his College of Physicians to appoint four people dedicated to inspecting what was being sold in apothecary shops. In conjunction with this first piece of legislation, there was an emergence of standard formulas for the creation of certain ‘drugs’ and ‘antidotes’ through Pharmacopoeias which first appeared in the form of a decree from Frederick II of Sicily in 1240 to use consistent and standard formulas; the first modern pharmacopoeias were the Florence Pharmacopoeia published in 1498, the Spanish Pharmacopoeia published in 1581 and the London Pharmacopoeia published in 1618. In the United States, regulation of drugs was a state right, as opposed to federal right.
But with the increase in fraudulent practices due to private incentives to maximize profits and poor enforcement of state laws, increased the need for stronger federal regulation. President Roosevelt signed the Federal Food and Drug Act in 1906 which established stricter standards. A 1911 Supreme Court decision, United States vs. Johnson, established that misleading statements were not covered under the FFDA; this directly led to Congress passing the Sherley Amendment which established a clearer definition of ‘misbranded’. Another key catalyst for advances in drug regulation were certain catastrophes that served as calls to the government to step in and impose regulations that would prevent repeats of those instances. One such instance occurred in 1937 when more than a hundred people died from using sulfanilamide elixir which had not gone through any safety testing; this directly led to the passing of the Federal, Food and Cosmetic Act in 1938. One other major catastrophe occurred in the late 1950s when Thalidomide, sold in Germany and sold around the world, led to 100,000 babies being born with various deformities.
The UK's Chief Medical Officer had established a group to look into safety of drugs on the market in 1959 prior to the crisis and was moving in the direction of address the problem of unregulated drugs entering the market. The crisis created a greater sense of emergency to establish safety and efficacy standards around the world; the UK started a temporary Committee on Safety of Drugs while they attempted to pass more comprehensive legislation. Though compliance and submission of drugs to the Committee on Safety of Drugs was not mandatory after, the pharmaceutical industry larger complied due to the thalidomide situation; the European Economic Commission passed a directive in 1965 in order to impose greater efficacy standards before marketing a drug. The United States congress passed the Drug Amendments Act of 1962 The Drug Amendments Act required the FDA to ensure that new drugs being introduced to the market had passed certain tests and standards. Both the EU and US acts introduced the requirements to ensure efficacy.
Of note, increased regulations and standards for testing led to greater innovation in pharm
Benzodiazepines, sometimes called "benzos", are a class of psychoactive drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. The first such drug, was discovered accidentally by Leo Sternbach in 1955, made available in 1960 by Hoffmann–La Roche, since 1963, has marketed the benzodiazepine diazepam. In 1977 benzodiazepines were globally the most prescribed medications, they are in the family of drugs known as minor tranquilizers. Benzodiazepines enhance the effect of the neurotransmitter gamma-aminobutyric acid at the GABAA receptor, resulting in sedative, anxiolytic and muscle relaxant properties. High doses of many shorter-acting benzodiazepines may cause anterograde amnesia and dissociation; these properties make benzodiazepines useful in treating anxiety, agitation, muscle spasms, alcohol withdrawal and as a premedication for medical or dental procedures. Benzodiazepines are categorized as either intermediary, or long-acting. Short- and intermediate-acting benzodiazepines are preferred for the treatment of insomnia.
Benzodiazepines are viewed as safe and effective for short-term use, although cognitive impairment and paradoxical effects such as aggression or behavioral disinhibition occur. A minority of people can have paradoxical reactions such as worsened panic. Benzodiazepines are associated with increased risk of suicide. Long-term use is controversial because of concerns about decreasing effectiveness, physical dependence, an increased risk of dementia. Stopping benzodiazepines leads to improved physical and mental health; the elderly are at an increased risk of both short- and long-term adverse effects, as a result, all benzodiazepines are listed in the Beers List of inappropriate medications for older adults. There is controversy concerning the safety of benzodiazepines in pregnancy. While they are not major teratogens, uncertainty remains as to whether they cause cleft palate in a small number of babies and whether neurobehavioural effects occur as a result of prenatal exposure. Benzodiazepines can cause dangerous deep unconsciousness.
However, they are less toxic than their predecessors, the barbiturates, death results when a benzodiazepine is the only drug taken. When combined with other central nervous system depressants such as alcoholic drinks and opioids, the potential for toxicity and fatal overdose increases. Benzodiazepines are misused and taken in combination with other drugs of abuse. Benzodiazepines possess psycholeptic, hypnotic, anticonvulsant, muscle relaxant, amnesic actions, which are useful in a variety of indications such as alcohol dependence, anxiety disorders, panic and insomnia. Most are administered orally. In general, benzodiazepines are well-tolerated and are safe and effective drugs in the short term for a wide range of conditions. Tolerance can develop to their effects and there is a risk of dependence, upon discontinuation a withdrawal syndrome may occur; these factors, combined with other possible secondary effects after prolonged use such as psychomotor, cognitive, or memory impairments, limit their long-term applicability.
The effects of long-term use or misuse include the tendency to cause or worsen cognitive deficits and anxiety. The College of Physicians and Surgeons of British Columbia recommends discontinuing the usage of benzodiazepines in those on opioids and those who have used them long term. Benzodiazepines can have serious adverse health outcomes, these findings support clinical and regulatory efforts to reduce usage in combination with non-benzodiazepine receptor agonists; because of their effectiveness and rapid onset of anxiolytic action, benzodiazepines are used for the treatment of anxiety associated with panic disorder. However, there is disagreement among expert bodies regarding the long-term use of benzodiazepines for panic disorder; the views range from those that hold that benzodiazepines are not effective long-term and that they should be reserved for treatment-resistant cases to those that hold that they are as effective in the long term as selective serotonin reuptake inhibitors. The American Psychiatric Association guidelines note that, in general, benzodiazepines are well tolerated, their use for the initial treatment for panic disorder is supported by numerous controlled trials.
APA states that there is insufficient evidence to recommend any of the established panic disorder treatments over another. The choice of treatment between benzodiazepines, SSRIs, serotonin–norepinephrine reuptake inhibitors, tricyclic antidepressants, psychotherapy should be based on the patient's history and other individual characteristics. Selective serotonin reuptake inhibitors are to be the best choice of pharmacotherapy for many patients with panic disorder, but benzodiazepines are often used, some studies suggest that these medications are still used with greater frequency than the SSRIs. One advantage of benzodiazepines is that they alleviate the anxiety symptoms much faster than antidepressants, therefore may be preferred in patients for whom rapid symptom control is critical. However, this advantage is offset by the possibility of developing benzodiazepine dependence. APA does not recommend benzodiazepines for persons with depressive
A carbamate is an organic compound derived from carbamic acid. A carbamate group, carbamate ester, carbamic acids are functional groups that are inter-related structurally and are interconverted chemically. Carbamate esters are called urethanes. Carbamic acids are unstable. For example, ammonium carbamate is generated by treatment of ammonia with carbon dioxide 2 NH3 + CO2 → NH4Carbamates arise via alcoholysis of chloroformamides: R2NCCl + R'OH → R2NCO2R' + HClAlternatively, cabamates can be formed from chloroformates and amines: R'OCCl + R2NH → R2NCO2R' + HClCarbamates may be formed from the Curtius rearrangement, where isocyanates formed are reacted with an alcohol. RCON3 → RNCO + N2 RNCO + R′OH → RNHCO2R′ Although most of this article concerns organic carbamates, the inorganic salt ammonium carbamate is produced on a large scale as an intermediate in the production of the commodity chemical urea from ammonia and carbon dioxide; the N-terminal amino groups of valine residues in the α- and β-chains of deoxyhemoglobin exist as carbamates.
They help to stabilise the protein, when it becomes deoxyhemoglobin and increases the likelihood of the release of remaining oxygen molecules bound to the protein. This stabilizing effect should not be confused with the Bohr effect; the ε-amino groups of the lysine residues in urease and phosphotriesterase feature carbamate. The carbamate derived from aminoimidazole is an intermediate in the biosynthesis of inosine. Carbamoyl phosphate is generated from carboxyphosphate rather than CO2; the most important carbamate is the one involved in the capture of CO2 by plants since this process is necessary for their growth. The enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase fixes a molecule of carbon dioxide as phosphoglycerate in the Calvin cycle. At the active site of the enzyme, a Mg2+ ion is bound to glutamate and aspartate residues as well as a lysine carbamate; the carbamate is formed when an uncharged lysine side chain near the ion reacts with a carbon dioxide molecule from the air, which renders it charged, therefore, able to bind the Mg2+ ion.
Some of the most common amine protecting groups, such as BOC, FMOC, Cbz and troc are carbamates. The so-called carbamate insecticides feature the carbamate ester functional group. Included in this group are aldicarb, carbaryl, fenobucarb and methomyl; these insecticides kill insects by reversibly inactivating the enzyme acetylcholinesterase. The organophosphate pesticides inhibit this enzyme, although irreversibly, cause a more severe form of cholinergic poisoning. Fenoxycarb has a carbamate group but acts as a juvenile hormone mimic, rather than inactivating acetylcholinesterase; the insect repellent icaridin is a substituted carbamate. Carbamate nerve agentsWhile the carbamate acetylcholinesterase inhibitors are referred to as "carbamate insecticides" due to their high selectivity for insect acetylcholinesterase enzymes over the mammalian versions, the most potent compounds such as aldicarb and carbofuran are still capable of inhibiting mammalian acetylcholinesterase enzymes at low enough concentrations that they pose a significant risk of poisoning to humans when used in large amounts for agricultural applications.
Other carbamate based acetylcholinesterase inhibitors are known with higher toxicity to humans, some such as T-1123 and EA-3990 were investigated for potential military use as nerve agents. However, since all compounds of this type have a quaternary ammonium group with a permanent positive charge, they have poor blood-brain barrier penetration, are only stable as crystalline salts or aqueous solutions, so were not considered to have suitable properties for weaponisation. Polyurethanes contain multiple carbamate groups as part of their structure; the "urethane" in the name "polyurethane" refers to these carbamate groups. In contrast, the substance called "urethane", ethyl carbamate, is neither a component of polyurethanes, nor is it used in their manufacture. Urethanes are formed by reaction of an alcohol with an isocyanate. Urethanes made by a non-isocyanate route are called carbamates. Polyurethane polymers have a wide range of properties and are commercially available as foams and solids. Polyurethane polymers are made by combining diisocyanates, e.g. toluene diisocyanate, diols, where the carbamate groups are formed by reaction of the alcohols with the isocyanates: RN=C=O + R′OH → RNHCOR′ Iodopropynyl butylcarbamate is a wood and paint preservative and used in cosmetics.
Urethane was once produced commercially in the United States as a chemotherapy agent and for other medicinal purposes. It was found to be toxic and ineffective, it is used as a veterinary medicine. In addition, some carbamates are used in human pharmacotherapy, for example, the acetylcholinesterase inhibitors neostigmine and rivastigmine, whose chemical structure is based on the natural alkaloid physostigmine. Other examples are meprobamate and its derivatives like carisoprodol, felbamate and tybamate, a class of anxiolytic and muscle relaxant drugs used in the 1960s before the rise of benzodiazepines, still used nowadays in some cases. Carbachol is used for various ophthalmic purposes; the protease inhibitor darunavir for HIV treatment contains a carbamate functional group. Carbamate insecticides target human melatonin receptors, along with inhibiting acetylcholi
Investigational New Drug
The United States Food and Drug Administration's Investigational New Drug program is the means by which a pharmaceutical company obtains permission to start human clinical trials and to ship an experimental drug across state lines before a marketing application for the drug has been approved. Regulations are at 21 C. F. R. 312. Similar procedures are followed in the European Union and Canada. Commercial INDs are filed by companies to obtain marketing approval for a new drug. Research or Investigator INDs are non-commercial INDs filed by researchers to study an unapproved drug or to study an approved drug for a new indication or in a new patient population. Emergency Use INDs called compassionate use or single-patient INDs, are filed for emergency use of an unapproved drug when the clinical situation does not allow sufficient time to submit an IND in accordance with 21 CFR §§ 312.23, 312.24. These are most used for life-threatening conditions for which there is no standard treatment. Treatment INDs are filed to make a drug available for treatment of serious or life-threatening conditions prior to FDA approval.
Serious diseases or conditions are stroke, rheumatoid arthritis, chronic depression, Alzheimer's dementia, amyotrophic lateral sclerosis, narcolepsy. Screening INDs are filed for multiple related compounds in order to screen for the preferred compounds or formulations; the preferred compound can be developed under a separate IND. Used for screening different salts and other drug derivatives that are chemically different, but pharmacodynamically similar; the IND application may be divided into the following categories: Preclinical Testing consists of animal pharmacology and toxicology studies to assess whether the drug is safe for testing in humans. Included are any previous experience with the drug in humans. Manufacturing Information includes composition and stability of, the controls used for, manufacturing the drug. Used to ensure that the company can adequately produce and supply consistent batches of the drug. Investigator Information on the qualifications of clinical investigators, that is, the professionals who oversee the administration of the experimental drug to the study subjects.
Used to assess whether the investigators are qualified to fulfill their clinical trial duties. Clinical Trial Protocols are the centerpiece of the IND. Detailed protocols for proposed clinical studies to assess whether the initial-phase trials will expose the subjects to unnecessary risks. Other Commitments are commitments to obtain informed consent from the research subjects, to obtain review of the study by an institutional review board, to adhere to the investigational new drug regulations. An IND must include an Investigator's Brochure intended to educate the trial investigators of the significant facts about the trial drug they need to know to conduct their clinical trial with the least hazard to the subjects or patients. Once an IND is submitted, the FDA has 30 days to object to the IND or it automatically becomes effective and clinical trials may begin. If the FDA detects a problem, it may place a clinical hold on the IND, prohibiting the start of the clinical studies until the problem is resolved.
Experimental drugs under an IND must be labeled "Caution: New Drug – Limited by Federal law to investigational use." Two thirds of both investigational new drugs and new drug applications are small-molecule drugs, the rest are biopharmaceuticals. About half of the investigational new drugs fail in preclinical and clinical phases of drug development; the FDA runs a medical marijuana IND program. It stopped accepting new patients in 1992 after public health authorities concluded there was no scientific value to it, due to President George H. W. Bush administration's desire to "get tough on crime and drugs." As of 2011, four patients continue to receive cannabis from the government under the program. Sanctioned by Executive Order 13139, the US Department of Defense employed an anthrax vaccine classified as an investigational new drug in its Anthrax Vaccine Immunization Program. Abigail Alliance for Better Access to Developmental Drugs Animal drug Drug discovery FDA Fast Track Development Program Good Manufacturing Practice Inverse benefit law New drug application, after clinical trials Biologics license application Orphan drug Investigational New Drug Application Process Center for Drug Evaluation and Research and Drug Administration.
ICH Guidance for Industry, E6 Good Clinical Practice: Consolidated Guidance. BROKEN LINK Troetel, W. M.: Achieving a Successful US IND Filing The Regulatory Affairs Journal. 6: 22–28, January 1995. Troetel, W. M.: Achieving a Successful US IND Filing The Regulatory Affairs Journal. 6: 104–108, February 1995. Henninger, Daniel. "Drug Lag". In David R. Henderson. Concise Encyclopedia of Economics. Library of Economics and Liberty. CS1 maint: Extra text: editors list OCLC 317650570, 50016270, 163149563 IND Forms and Instructions from the US Food and Drug Administration
Oxazepam is a short-to-intermediate-acting benzodiazepine. Oxazepam is used for the treatment of anxiety and insomnia and in the control of symptoms of alcohol withdrawal syndrome, it is a metabolite of diazepam and temazepam, has moderate amnesic, anticonvulsant, hypnotic and skeletal muscle relaxant properties compared to other benzodiazepines. It was patented in 1962 and approved for medical use in 1964, it is an intermediate-acting benzodiazepine with a slow onset of action, so it is prescribed to individuals who have trouble staying asleep, rather than falling asleep. It is prescribed for anxiety disorders with associated tension and agitation, it is prescribed for drug and alcohol withdrawal, for anxiety associated with depression. Physicians may use oxazepam outside its approved indications to treat social phobia, post-traumatic stress disorder, premenstrual syndrome, other conditions; the side effects of oxazepam are similar to those of other benzodiazepines, may include dizziness, headache, memory impairment, paradoxical excitement, anterograde amnesia, but does not affect transient global amnesia.
Side effects due to rapid decrease in dose or abrupt withdrawal from oxazepam may include abdominal and muscle cramps, depression, inability to fall asleep or stay asleep, tremors, or vomiting. Oxazepam, as with other benzodiazepine drugs, can cause tolerance, physical dependence and benzodiazepine withdrawal syndrome. Withdrawal from oxazepam or other benzodiazepines leads to withdrawal symptoms which are similar to those seen during alcohol and barbiturate withdrawal; the higher the dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can occur, though, at standard dosages and after short-term use. Benzodiazepine treatment should be discontinued as soon as possible by a slow and gradual dose reduction regimen. Oxazepam is contraindicated in myasthenia gravis, chronic obstructive pulmonary disease, limited pulmonary reserve, as well as severe hepatic disease. Benzodiazepines require special precautions if used in the elderly, during pregnancy, in children, alcohol- or drug-dependent individuals, individuals with comorbid psychiatric disorders.
Benzodiazepines including oxazepam are lipophilic drugs and penetrate membranes, so crosses over into the placenta with significant uptake of the drug. Use of benzodiazepines in late pregnancy high doses, may result in floppy infant syndrome. Oxazepam when taken during late in pregnancy, the third trimester, causes a definite risk to the neonate including a severe benzodiazepine withdrawal syndrome including hypotonia, reluctance to suck, to apnoeic spells and impaired metabolic responses to cold stress. Floppy infant syndrome and sedation in the newborn may occur. Symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth; as oxazepam is an active metabolite of diazepam, an overlap in possible interactions is with other drugs or food, with exception of the pharmacokinetic CYP450 interactions. Precautions and following the prescription are required when taking oxazepam in combinations with antidepressant medication, potent painkillers.
Concurrent use of these medicines can interact in a way, difficult to predict. Drinking alcohol when taking oxazepam is not recommended. Concomitant use of oxazepam and alcohol can lead to increased sedation, severe problems with coordination, decreased muscle tone, in severe cases or in predisposed patients to life-threatening intoxications with respiratory depression and collapse. Oxazepam is less toxic in overdose than other benzodiazepines. Important factors which affect the severity of a benzodiazepine overdose include the dose ingested, the age of the patient, health status prior to overdose. Benzodiazepine overdoses can be much more dangerous if a coingestion of other CNS depressants such as opiates or alcohol has occurred. Symptoms of an oxazepam overdose include: Respiratory depression Excessive somnolence Altered consciousness Central nervous system depression Occasionally cardiovascular and pulmonary toxicity Rarely, deep coma Oxazepam is an intermediate-acting benzodiazepine of the 3-hydroxy family.
The half-life of oxazepam is four to 15 hours. It has been shown to suppress cortisol levels. Oxazepam is the most absorbed and has the slowest onset of action of all the common benzodiazepines according to one British study. Oxazepam is an active metabolite formed during the breakdown of diazepam and certain similar drugs, it may be safer than many other benzodiazepines in patients with impaired liver function because it does not require hepatic oxidation, but rather, it is metabolized by glucuronidation, so oxazepam is less to accumulate and cause adverse reactions in the elderly or people with liver disease. Oxazepam is similar to lorazepam in this respect. Preferential storage of oxazepam occurs in some organs, including the heart of the neonate. Absorption by any administered route and the risk of accumulation is increased in the neonate, withdrawal of oxazepam during pregnancy and breast feedin
The Jmol applet, among other abilities, offers an alternative to the Chime plug-in, no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, the Sculpt mode. Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS 9. Jmol operates on a wide variety of platforms. For example, Jmol is functional in Mozilla Firefox, Internet Explorer, Google Chrome, Safari. Chemistry Development Kit Comparison of software for molecular mechanics modeling Jmol extension for MediaWiki List of molecular graphics systems Molecular graphics Molecule editor Proteopedia PyMOL SAMSON Official website Wiki with listings of websites and moodles Willighagen, Egon. "Fast and Scriptable Molecular Graphics in Web Browsers without Java3D". Doi:10.1038/npre.2007.50.1