Pathways

Ketamine is a rapid acting general anesthetic and NMDA receptor antagonist. It was developed in 1963 as a replacement for phencyclidine (PCP). It was used for veterinary purposes in Belgium. In 1970, it was approved by the FDA after in 1964 it was proven to only produce minor hallucinogenic effects and shorter psychotomimetic effects compared to PCP. Ketamine acts on NMDA receptors, opioid receptors, monoaminergic receptors, muscarinic receptors and voltage sensitive Ca ion channels. Ketamine is injected intravenously or intramuscularly then diffuses into the brain across the blood-brain barrier. Ketamine antagonizes NMDA receptors at the 3A subunit. This prevents glutamate form activating the receptor and calcium from entering the postsynaptic neuron. This causes hyperpolarization of the neuron and prevents depolarization. This leads to an anaesthesia and analgesia.

Metabolites of Ketamine are predicted with biotransformer.

Ketazolam is a long-acting benzodiazepine used to manage anxiety and insomnia. Ketazolam is a benzodiazepine derivative with anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant activity. Ketazolam is not approved in Canada or America. It can be found under the brand names Anseren, Ansieten, Marcen, and Solatran. Benzodiazepines enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA), which results in sedative, hypnotic, anxiolytic, anticonvulsant, muscle relaxant and amnesic action. Benzodiazepines bind nonspecifically to benzodiazepine receptors which mediate sleep, affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell. Benzodiazepines share a similar chemical structure and their effects in humans are mainly produced by the allosteric modification of a specific kind of neurotransmitter receptor, the GABAA receptor, which increases the conductance of this inhibitory channel; this results in the various therapeutic effects as well as adverse effects of benzodiazepines. Binding of benzodiazepines to this receptor complex promotes binding of GABA, which in turn increases the conduction of chloride ions across the neuronal cell membrane. This increased conductance raises the membrane potential of the neuron resulting in inhibition of neuronal firing. In addition, different GABAA receptor subtypes have varying distributions within different regions of the brain and therefore control distinct neuronal circuits. Hence, activation of different GABAA receptor subtypes by benzodiazepines may result in distinct pharmacological actions. Some side effects of using ketazolam may include depression, anxiety, diarrhea, and confusion.

Metabolites of Ketazolam are predicted with biotransformer.

Ketobemidone is an opioid analgesic and is used to treat severe pain such as postoperative, cancer, fractures and kidney stones. It has some NMDA antagonist properties. It is administered intravenously, orally and rectal, and is mainly only used in Scandinavian countries. Compared to morphine it is more effective for analgesia and has a reduced risk of addiction under supervision. Ketobemidone is metabolized by conjugation of phenolic hydroxyl group and by N-methylation, with only roughly 24% excreted unchanged after intravenous administration.

Ketobemidone (also known as Ketogan) is analgesic that can bind to mu-type opioid receptor to activate associated G-protein in the sensory neurons of central nervous system (CNS), which will reduce the level of intracellular cAMP by inhibiting adenylate cyclase. The binding of ketobemidone acetate will eventually lead to reduced pain because of decreased nerve conduction and release of neurotransmitter. Hyperpolarization of neuron is caused by inactivation of calcium channels and activation of potassium channels via facilitated by G-protein.