Zolazepam

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Zolazepam
Zolazepam.svg
Zolazepam3d.png
Clinical data
Trade names Telazol (in combination with tiletamine)
AHFS/Drugs.com International Drug Names
ATC code
  • none
Legal status
Legal status
Identifiers
  • 4-(2-fluorophenyl)-1,3,8-trimethyl-6H-pyrazolo[3,4-e][1,4]diazepin-7-one
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard 100.118.306 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C15H15FN4O
Molar mass 286.310 g·mol−1
3D model (JSmol)
  • FC1=CC=CC=C1C2=NCC(N(C)C3=C2C(C)=NN3C)=O
  • InChI=1S/C15H15FN4O/c1-9-13-14(10-6-4-5-7-11(10)16)17-8-12(21)19(2)15(13)20(3)18-9/h4-7H,8H2,1-3H3 Yes check.svgY
  • Key:GDSCFOSHSOWNDL-UHFFFAOYSA-N Yes check.svgY
   (verify)

Zolazepam [2] (Flupyrazapon) is a pyrazolodiazepinone derivative structurally related to the benzodiazepine drugs, which is used as an anaesthetic for a wide range of animals in veterinary medicine. Zolazepam is usually administered in combination with other drugs such as the NMDA antagonist tiletamine or the α2 adrenergic receptor agonist xylazine, depending on what purpose it is being used for. It is 5-10 times the potency of diazepam. [3]

Zolazepam was developed by Horace A. de Wald and Donald E. Butler for Parke-Davis [4] and was the result of a very detailed analysis of the benzodiazepine structure ( U.S. patent 3,558,605 filed in 1969).

Zolazepam, in combination with tiletamine, has been used in the tranquilization of wild animals, such as gorillas and polar bears, and has been found to be superior to ketamine because of reduced side-effects. [5] [6] A 1:1 mixture of zolazepam and tiletamine is sold under the names Telazol and Zoletil.

See also

Related Research Articles

<span class="mw-page-title-main">Flunitrazepam</span> Benzodiazepine sedative

Flunitrazepam, sold under the brand name Rohypnol among others, is a benzodiazepine used to treat severe insomnia and assist with anesthesia. As with other hypnotics, flunitrazepam has been advised to be prescribed only for short-term use or by those with chronic insomnia on an occasional basis.

<span class="mw-page-title-main">Ketamine</span> Dissociative anesthetic and anti-depressant

Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a treatment for depression and pain management. It is a novel compound that was derived from phencyclidine in 1962 in pursuit of a safer anesthetic with fewer hallucinogenic effects.

Dissociatives, colloquially dissos, are a subclass of hallucinogens that distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of such action, dissociatives are unique in that they do so in such a way that they produce hallucinogenic effects, which may include dissociation, a general decrease in sensory experience, hallucinations, dream-like states or anesthesia. Despite most dissociatives' main mechanism of action being tied to NMDA receptor antagonism, some of these substances, which are nonselective in action and affect the dopamine and/or opioid systems, may be capable of inducing more direct and repeatable euphoria or symptoms which are more akin to the effects of typical "hard drugs" or common drugs of abuse. This is likely why dissociatives are considered to be addictive with a fair to moderate potential for abuse, unlike psychedelics. Despite some dissociatives, such as phencyclidine (PCP) possessing stimulating properties, most dissociatives seem to have a general depressant effect and can produce sedation, respiratory depression, nausea, disorientation, analgesia, anesthesia, ataxia, cognitive and memory impairment as well as amnesia.

<span class="mw-page-title-main">Midazolam</span> Benzodiazepine used for anesthesia and procedural sedation

Midazolam, sold under the brand name Versed among others, is a benzodiazepine medication used for anesthesia, premedication before surgical anesthesia, and procedural sedation, and to treat severe agitation. It induces sleepiness, decreases anxiety, and causes anterograde amnesia.

<span class="mw-page-title-main">Anesthetic</span> Drug that causes anesthesia

An anesthetic or anaesthetic is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two broad classes: general anesthetics, which result in a reversible loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for a limited region of the body without necessarily affecting consciousness.

<i>Controlled Drugs and Substances Act</i> Canadian federal drug regulation act

The Controlled Drugs and Substances Act is Canada's federal drug control statute. Passed in 1996 under Prime Minister Jean Chrétien's government, it repeals the Narcotic Control Act and Parts III and IV of the Food and Drugs Act, and establishes eight Schedules of controlled substances and two Classes of precursors. It provides that "The Governor in Council may, by order, amend any of Schedules I to VIII by adding to them or deleting from them any item or portion of an item, where the Governor in Council deems the amendment to be necessary in the public interest."

<span class="mw-page-title-main">Tiletamine</span> Chemical compound

Tiletamine is a dissociative anesthetic and pharmacologically classified as an NMDA receptor antagonist. It is related chemically to ketamine. Tiletamine hydrochloride exists as odorless white crystals.

<span class="mw-page-title-main">Tofisopam</span> Anxiolytic medication

Tofisopam is an anxiolytic that is marketed in several European countries. Chemically, it is a 2,3-benzodiazepine. Unlike other anxiolytic benzodiazepines however, tofisopam does not have anticonvulsant, sedative, skeletal muscle relaxant, motor skill-impairing or amnestic properties. While it may not be an anticonvulsant in and of itself, it has been shown to enhance the anticonvulsant action of classical 1,4-benzodiazepines and muscimol, but not sodium valproate, carbamazepine, phenobarbital, or phenytoin. Tofisopam is indicated for the treatment of anxiety and alcohol withdrawal, and is prescribed in a dosage of 50–300 mg per day divided into three doses. Peak plasma levels are attained two hours after an oral dose. Tofisopam is not reported as causing dependence to the same extent as other benzodiazepines, but is still recommended to be prescribed for a maximum of 12 weeks.

<span class="mw-page-title-main">Veterinary surgery</span> Surgery performed on non-human animals

Veterinary surgery is surgery performed on non-human animals by veterinarians, whereby the procedures fall into three broad categories: orthopaedics, soft tissue surgery, and neurosurgery. Advanced surgical procedures such as joint replacement, fracture repair, stabilization of cranial cruciate ligament deficiency, oncologic (cancer) surgery, herniated disc treatment, complicated gastrointestinal or urogenital procedures, kidney transplant, skin grafts, complicated wound management, and minimally invasive procedures are performed by veterinary surgeons. Most general practice veterinarians perform routine surgeries such as neuters and minor mass excisions; some also perform additional procedures.

<span class="mw-page-title-main">NMDA receptor antagonist</span> Class of anesthetics

NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the N-Methyl-D-aspartate receptor (NMDAR). They are commonly used as anesthetics for humans and animals; the state of anesthesia they induce is referred to as dissociative anesthesia.

<span class="mw-page-title-main">Azaperone</span> Chemical compound

Azaperone is a pyridinylpiperazine and butyrophenone neuroleptic drug with sedative and antiemetic effects, which is used mainly as a tranquilizer in veterinary medicine. It is uncommonly used in humans as an antipsychotic drug.

Veterinary anesthesia is a specialization in the veterinary medicine field dedicated to the proper administration of anesthetic agents to non-human animals to control their consciousness during procedures. A veterinarian or a Registered Veterinary Technician administers these drugs to minimize stress, destructive behavior, and the threat of injury to both the patient and the doctor. The duration of the anesthesia process goes from the time before an animal leaves for the visit to the time after the animal reaches home after the visit, meaning it includes care from both the owner and the veterinary staff. Generally, anesthesia is used for a wider range of circumstances in animals than in people not only due to their inability to cooperate with certain diagnostic or therapeutic procedures, but also due to their species, breed, size, and corresponding anatomy. Veterinary anesthesia includes anesthesia of the major species: dogs, cats, horses, cattle, sheep, goats, and pigs, as well as all other animals requiring veterinary care such as birds, pocket pets, and wildlife.

<span class="mw-page-title-main">Medetomidine</span> Chemical compound

Medetomidine is a synthetic drug used as both a surgical anesthetic and analgesic. It is often used as the hydrochloride salt, medetomidine hydrochloride, a crystalline white solid. It is an α2 adrenergic agonist that can be administered as an intravenous drug solution with sterile water.

<span class="mw-page-title-main">Etoxadrol</span> Chemical compound

Etoxadrol (CL-1848C) is a dissociative anaesthetic drug that has been found to be an NMDA antagonist and produce similar effects to PCP in animals. Etoxadrol, along with another related drug dexoxadrol, were developed as analgesics for use in humans, but development was discontinued in the late 1970s after patients reported side effects such as nightmares and hallucinations.

<span class="mw-page-title-main">Atipamezole</span> Veterinary medication

Atipamezole, sold under the brand name Antisedan among others, is a synthetic α2 adrenergic receptor antagonist used for the reversal of the sedative and analgesic effects of dexmedetomidine and medetomidine in dogs. Its reversal effect works by competing with the sedative for α2-adrenergic receptors and displacing them. It is mainly used in veterinary medicine, and while it is only licensed for dogs and for intramuscular use, it has been used intravenously, as well as in cats and other animals(intravenous use in cats and dogs is not recommended due to the potential for cardiovascular collapse. This occurs due to profound hypotension caused by reversal of the alpha 1 effects while the reflex bradycardia is still in effect.). There is a low rate of side effects, largely due to atipamezole's high specificity for the α2-adrenergic receptor. Atipamezole has a very quick onset, usually waking an animal up within 5 to 10 minutes.

<span class="mw-page-title-main">Romifidine</span> Chemical compound

Romifidine is a drug that is used in veterinary medicine as a sedative mainly in large animals such as horses, although it may be used in a wide variety of species. It is not used in humans, but is closely related in structure to the commonly used drug clonidine.

<span class="mw-page-title-main">Sarmazenil</span> Chemical compound

Sarmazenil (Ro15-3505) is a drug from the benzodiazepine family. It acts as a partial inverse agonist of benzodiazepine receptors, meaning that it causes the opposite effects to most benzodiazepine drugs, and instead acts as an anxiogenic and convulsant. It is used in veterinary medicine to reverse the effects of benzodiazepine sedative drugs in order to rapidly re-awaken anesthetized animals.

<span class="mw-page-title-main">Climazolam</span> Anesthetic drug

Climazolam (Ro21-3982) was introduced under licence as a veterinary medicine by the Swiss Pharmaceutical company Gräub under the tradename Climasol. Climazolam is a benzodiazepine, specifically an imidazobenzodiazepine derivative developed by Hoffman-LaRoche. It is similar in structure to midazolam and diclazepam and is used in veterinary medicine for anesthetizing animals.

These drugs are known in the UK as controlled drug, because this is the term by which the act itself refers to them. In more general terms, however, many of these drugs are also controlled by the Medicines Act 1968, there are many other drugs which are controlled by the Medicines Act but not by the Misuse of Drugs Act, and some other drugs are controlled by other laws.

<span class="mw-page-title-main">Balanced anesthesia</span> Anesthetic technique

Balanced anesthesia is an anesthetic method for surgical patients during their operation. The method was proposed by John Lundy in 1926. The purpose of balanced anesthesia is to use multiple anesthetic agents for a safer general anesthesia and to mitigate the potential adverse side effects which may be caused by the anesthetic agents. The concept of balanced anesthesia is that of applying two or more medications or techniques in order to ease pain, relax the muscles, and have autonomous reflexes suppressed in the patient. In other words, it is an anesthesia method to maintain stable vital signs. There are numerous factors that come into play when the anesthetist decides to use this method of anesthesia. These factors include, but are not limited to: patients' major organ functions, general condition and compensatory capacity. By making use of adequate types and appropriate amounts of agents and accurate anesthesia methods, the anesthetist will promote a successful, safe, and efficient surgery.

References

  1. "Schedules of Controlled Substances: Placement of Preparations Which Contain Both Tiletamine and Zolazepam into Schedule III" (PDF). Isomer Design. Drug Enforcement Administration. January 21, 1987. Archived (PDF) from the original on March 3, 2022. Retrieved January 16, 2023.
  2. US 3879535,Stoliker, Harry E.,"Anesthetic compositions and methods of use",published 1975-04-22, assigned to Parke, Davis & Co.
  3. DeWald HA, Lobbestael S, Butler DE (December 1977). "Pyrazolodiazepines. 2. 4-Aryl-1,3-dialkyl-6,8-dihydropyrazolo[3,4-e] [1,4]diazepin-7(1H)-ones as antianxiety and anticonvulsant agents". Journal of Medicinal Chemistry. 20 (12): 1562–9. doi:10.1021/jm00222a005. PMID   22748.
  4. DE 2023453,DeWald, Horace Albert&Butler, Donald Eugene,"Pyrazolo[3,4-e],[1,4]diazepin-7(1H)-on Verbindungen und ihre pharmazeutisch zulässigen Salze [Pyrazolo[3,4-e],[1.4]diazepin-7(lH)-one compounds and their pharmaceutically acceptable salts]",published 1970-11-19, assigned to Parke, Davis & Co.
  5. Sleeman JM, Cameron K, Mudakikwa AB, Nizeyi JB, Anderson S, Cooper JE, et al. (March 2000). "Field anesthesia of free-living mountain gorillas (Gorilla gorilla beringei) from the Virunga Volcano region, Central Africa". Journal of Zoo and Wildlife Medicine. 31 (1): 9–14. doi:10.1638/1042-7260(2000)031[0009:faoflm]2.0.co;2. PMID   10884117. S2CID   20623485.
  6. Cattet MR, Caulkett NA, Polischuk SC, Ramsay MA (September 1999). "Anesthesia of polar bears (Ursus maritimus) with zolazepam-tiletamine, medetomidine-ketamine, and medetomidine-zolazepam-tiletamine". Journal of Zoo and Wildlife Medicine. 30 (3): 354–60. PMID   10572857.