General anaesthetics are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include an induced coma that causes lack of awareness to painful stimuli, sufficient to facilitate surgical applications in clinical and veterinary practice. General anaesthetics do not act as analgesics and should also not be confused with sedatives. General anaesthetics are a structurally diverse group of compounds whose mechanisms encompass multiple biological targets involved in the control of neuronal pathways. The precise workings are the subject of some debate and ongoing research.
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. Ketamine is a novel compound that was derived from phencyclidine in 1962 in pursuit of a safer anesthetic with fewer hallucinogenic effects.
Phencyclidine or phenylcyclohexyl piperidine (PCP), also known in its use as a street drug as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hallucinations, distorted perceptions of sounds, and violent behavior. As a recreational drug, it is typically smoked, but may be taken by mouth, snorted, or injected. It may also be mixed with cannabis or tobacco.
Propofol is the active component of an intravenous anesthetic formulation used for induction and maintenance of general anesthesia. It is chemically termed 2,6-diisopropylphenol. The formulation was originally approved under the brand name Diprivan. Numerous generic offerings of this formulation now exist. Intravenous administration is used to induce unconsciousness after which anesthesia may be maintained using a combination of medications. It is manufactured as part of a sterile injectable emulsion formulation using soybean oil and lecithin, giving it a white milky coloration.
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.
Levobupivacaine (rINN) is a local anaesthetic drug indicated for minor and major surgical anaesthesia and pain management. It is a long-acting amide-type local anaesthetic that blocks nerve impulses by inhibiting sodium ion influx into the nerve cells. Levobupivacaine is the S-enantiomer of racemic bupivacaine and therefore similar in pharmacological effects. The drug typically starts taking effect within 15 minutes and can last up to 16 hours depending on factors such as site of administration and dosage.
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 human and non-human animals; the state of anesthesia they induce is referred to as dissociative anesthesia.
(+)-CPCA is a stimulant drug similar in structure to pethidine and to RTI-31, but nocaine is lacking the two-carbon bridge of RTI-31's tropane skeleton. This compound was first developed as a substitute agent for cocaine.
Lofentanil or lofentanyl is one of the most potent opioid analgesics known and is an analogue of fentanyl, which was developed in 1960. It is most similar to the highly potent opioid carfentanil (4-carbomethoxyfentanyl), only slightly more potent. Lofentanil can be described as 3-methylcarfentanil, or 3-methyl-4-carbomethoxyfentanyl. While 3-methylfentanyl is considerably more potent than fentanyl itself, lofentanil is only slightly stronger than carfentanil. This suggests that substitution at both the 3 and 4 positions of the piperidine ring introduces steric hindrance which prevents μ-opioid affinity from increasing much further. As with other 3-substituted fentanyl derivatives such as ohmefentanyl, the stereoisomerism of lofentanil is very important, with some stereoisomers being much more potent than others.
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.
Dimethocaine, also known as DMC or larocaine, is a compound with a stimulatory effect. This effect resembles that of cocaine, although dimethocaine appears to be less potent. Just like cocaine, dimethocaine is addictive due to its stimulation of the reward pathway in the brain. However, dimethocaine is a legal cocaine replacement in some countries and is even listed by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) under the category “synthetic cocaine derivatives”. The structure of dimethocaine, being a 4-aminobenzoic acid ester, resembles that of procaine. It is found as a white powder at room temperature.
3β-(p-Fluorobenzoyloxy)tropane, (8-Methyl-8-azabicyclo[3.2.1]oct-3-yl 4-fluorobenzoic acid ester, 4-fluorotropacocaine, 3-Pseudotropyl-4-fluorobenzoate, 3-pseudotropyl-4-fluorobenzoate, pFBT) is a tropane derivative drug which acts as a local anaesthetic, having around 30% the stimulant potency of cocaine but around the same potency as a local anaesthetic. It has been investigated as a potential radiolabelled agent for studying receptor binding, but was not adopted for this application. The main application for fluorotropacocaine, however, has been as a designer drug analogue of cocaine, first detected by the EMCDDA in 2008, and subsequently sold as an ingredient of various "bath salt" powder products, usually mixed in combination with other stimulant drugs such as caffeine, dimethocaine, desoxypipradrol or substituted cathinone derivatives.
RTI(-4229)-113 is a stimulant drug which acts as a potent and fully selective dopamine reuptake inhibitor (DRI). It has been suggested as a possible substitute drug for the treatment of cocaine addiction. "RTI-113 has properties that make it an ideal medication for cocaine abusers, such as an equivalent efficacy, a higher potency, and a longer duration of action as compared to cocaine." Replacing the methyl ester in RTI-31 with a phenyl ester makes the resultant RTI-113 fully DAT specific. RTI-113 is a particularly relevant phenyltropane cocaine analog that has been tested on squirrel monkeys. RTI-113 has also been tested against cocaine in self-administration studies for DAT occupancy by PET on awake rhesus monkeys. The efficacy of cocaine analogs to elicit self-administration is closely related to the rate at which they are administered. Slower onset of action analogs are less likely to function as positive reinforcers than analogues that have a faster rate of onset.
Arylcyclohexylamines, also known as arylcyclohexamines or arylcyclohexanamines, are a chemical class of pharmaceutical, designer, and experimental drugs.
3-Methoxyphencyclidine (3-MeO-PCP) is a dissociative hallucinogen of the arylcyclohexylamine class related to phencyclidine (PCP) which has been sold online as a designer drug. It acts mainly as an NMDA receptor antagonist, though it has also been found to interact with the sigma σ1 receptor and the serotonin transporter. The drug does not possess any opioid activity nor does it act as a dopamine reuptake inhibitor.
4-Methoxyphencyclidine is a dissociative anesthetic drug that has been sold online as a research chemical. The synthesis of 4-MeO-PCP was first reported in 1965 by the Parke-Davis medicinal chemist Victor Maddox. A 1999 review published by a chemist using the pseudonym John Q. Beagle suggested the potency of 4-MeO-PCP in man was reduced relative to PCP, two years later Beagle published a detailed description of the synthesis and qualitative effects of 4-MeO-PCP, which he said possessed 70% the potency of PCP. 4-MeO-PCP was the first arylcyclohexylamine research chemical to be sold online, it was introduced in late 2008 by a company trading under the name CBAY and was followed by several related compounds such as 3-MeO-PCP and methoxetamine. 4-MeO-PCP has lower affinity for the NMDA receptor than PCP, but higher affinity than ketamine, it is orally active in a dosage range similar to ketamine, with some users requiring doses in excess of 100 mg for desired effects. Users have reported substantial differences in active dose, these discrepancies can be partially explained by the presence of unreacted PCC and other impurities in samples sold on the grey market. 4-MeO-PCP has Ki values of 404 nM for the NMDA receptor, 713 nM for the norepinephrine transporter, 844 nM for the serotonin transporter, 296 nM for the σ1 receptor and 143 nM for the σ2 receptor.
Arketamine (developmental code names PCN-101, HR-071603), also known as (R)-ketamine or (R)-(−)-ketamine, is the (R)-(−) enantiomer of ketamine. Similarly to racemic ketamine and esketamine, the S(+) enantiomer of ketamine, arketamine is biologically active; however, it is less potent as an NMDA receptor antagonist and anesthetic and thus has never been approved or marketed for clinical use as an enantiopure drug. Arketamine is currently in clinical development as a novel antidepressant.
Thiafentanil is a highly potent opioid analgesic that is an analog of fentanyl, and was invented in 1986. Its analgesic potency is slightly less than that of carfentanil, though with a faster onset of effects, shorter duration of action and a slightly lesser tendency to produce respiratory depression. It is used in veterinary medicine to anesthetise animals such as impala, usually in combination with other anesthetics such as ketamine, xylazine or medetomidine to reduce the prevalence of side effects such as muscle rigidity.
AM-7438 is a drug which is a cannabinoid receptor agonist, developed by the research team led by Dr Alexandros Makriyannis. It is a derivative of Δ8-THC which has been substituted with a side chain containing a metabolically labile ester group, allowing the molecule to be rapidly metabolised to an inactive form, in a similar manner to drugs such as remifentanil, remimazolam and SN 35210. This means that while AM-7438 retains potent cannabinoid effects, it has a much shorter duration of action than most related compounds.
1-(2-Chloro-N-methylbenzimidoyl)cyclopentanol, sometimes misleadingly referred to as hydroxylimine hydrochloride, is a chemical compound which is the final intermediate in the synthesis of ketamine, an anaesthetic drug which is also subject to recreational abuse. This chemical intermediate is not active as a drug in its own right, and is legal in most countries, but is readily converted into ketamine by dissolving it in a suitable high-boiling point solvent and heating, with no other chemicals required. This has made it subject to illicit trade as a drug precursor, and it has sometimes been seized by law enforcement agencies in significant quantities, leading to it being specifically banned as a controlled drug precursor in some jurisdictions such as Taiwan.
