Dimethocaine
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| Other names | DMC, larocaine |
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| Density | 1.0±0.1 g/cm3 (predicted) |
| Melting point | 48 to 51 °C (118 to 124 °F) (experimental) |
| Boiling point | 334 to 403 °C (633 to 757 °F) at 760 mmHg |
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Dimethocaine, also known as DMC or larocaine, is a compound with a stimulatory effect. This effect resembles that of
When a product sold online in the UK in June 2010, advertised as dimethocaine was tested, it was found to be a mixture of caffeine and lidocaine,[3] and the lack of any dopaminergic stimulant ingredient in such mixes may explain the limited recreational effects reported by many users. Other samples tested have however been shown to contain genuine dimethocaine, and one branded "bath salt" product containing primarily dimethocaine as the active ingredient, was noted to have been particularly subject to abuse by intravenous drug users in Ireland.[4]
History
Dimethocaine was originally synthesized by the
Pharmacology
Pharmacodynamics
Dimethocaine and structurally related local anesthetics such as cocaine and procaine inhibit the uptake of dopamine (DA) by blocking dopamine transporters (DAT).[7] The dopamine transporter controls the dynamics of the neurotransmitter dopamine. This neurotransmitter controls many functions including movement, cognition and mood. Drugs such as cocaine and dimethocaine induce dopamine overflow by inhibiting dopamine transporters and thus creating a euphoric effect.[8] In addition to inhibiting dopamine uptake, dimethocaine was also shown to inhibit the binding of CFT, a different dopamine uptake inhibitor.[7] These inhibitory properties are responsible for the stimulatory effects of dimethocaine on the central nervous system.[5] Both in vivo and in vitro measurements of dopamine transporter activity showed that dimethocaine is a potent and efficacious dopaminergic reuptake inhibitor (also called a dopamine indirect agonist).[7] These effects were mainly observed in the nucleus accumbens, a region in the basal forebrain.[5] Comparison of the pharmacological potencies of different local anesthetics revealed the following potency order:[5]
cocaine > dimethocaine > tetracaine > procaine > chloroprocaine
Furthermore, the administration of dimethocaine has been shown to lead to antinociceptive responses at nontoxic doses in mice.[9] These responses are suggested to be at least partially caused by the effects of dimethocaine on the central nervous system. A memory impairing effect observed in mice after administration of dimethocaine has been proposed to be a result of a non-anesthetic mechanism of action.[10]
Pharmacokinetics
When inhaled, dimethocaine starts working in 10–30 minutes, with highest effects at 60–120 minutes and until 4–6 hours there is a period of action with the ‘after-effects’.[11] The after effects include fatigue and slight mental impairment.[6]
Metabolism
The exact metabolic pathways of dimethocaine have not been researched, but the different metabolites have been examined in Wistar rats. After administration of dimethocaine, different metabolites have been found and identified in their urine. Due to these metabolites, different metabolic pathways could have been postulated. The main phase I reactions are ester hydrolysis, deethylation, hydroxylation of the aromatic system, or a combination of these three.[1] The main phase II reactions are N-acetylation, glucuronidation and a combination of both.[5][1] Different cytochrome P450 isozymes are involved in the initial steps of human metabolism. The N-acetylation is catalyzed by the NAT2 isozyme.[12]
Efficacy and side effects
Just like cocaine, dimethocaine inhibits the uptake of dopamine in the brain by interfering with the dopamine transporters.[13] The potency of these drugs is linked to their affinity for the dopamine transporters, and their potency to inhibit dopamine uptake.[7]
In studies with rhesus monkeys the affinity of dimethocaine for dopamine transporters is smaller than that of cocaine, whereas dimethocaine's potency to inhibit dopamine uptake is similar. This means that more of dimethocaine is needed to reach a similar response. The peak effects occurred within 10 to 20 minutes after the injection and decreased to baseline levels within an hour.[13]
Dimethocaine is often abused as a legal substitute for cocaine. The drug is administered intravenously or nasally, because ingestion would lead to rapid hydrolyzation.[5] Its positive effects are euphoria, stimulation, increased talkativeness and mood lift.[6] However, because the drug acts similar as cocaine, it has comparable negative side effects. These side effects include: tachycardia, difficulty with breathing, pain on the chest, vasoconstriction, insomnia, paranoia and anxiety.[6] Dimethocaine probably poses larger health issues than cocaine. This is due to the fact that more dimethocaine must be administered to produce the same euphoric feeling, resulting in larger risk for the negative effects.
Toxicity
Humans
Cocaine and other local anesthetics are known to produce cardiotoxicity by blocking sodium channels. However, no reports have been published of these same effects of cardiotoxicity associated with dimethocaine.[2] There has been little research about toxicity of dimethocaine in humans, and therefore the exact lethal or pharmacological doses are unknown.
Animals
For mice, the dose at which acute toxicity occurs for intravenous administration is 40 mg/kg and for
An abdominal constriction test was performed in mice, using doses of 5, 10, and 20 mg/kg of dimethocaine which were administered subcutaneously. This test showed induced dose-dependent antinociceptive responses, which are processes that block detection of a painful or injurious stimulus by sensory neurons.[9]
Impairment of memory processes was found to be a toxic effect in the elevated plus-maze test in mice.[10]
Legal status
Sweden's public health agency suggested classifying Dimethocaine as a hazardous substance, on September 25, 2019.[16]
See also
References
- ^ S2CID 10850370.
- ^ ISBN 978-0-12-415911-2.
- S2CID 20354123.
- ^ An overview of new psychoactive substances and the outlets supplying them Archived November 25, 2011, at the Wayback Machine
- ^ a b c d e f Lindauer C (2014). Toxicokinetics of Emerging Drugs of Abuse: In vivo and in vitro studies on the metabolic fate of the cocaine-derived designer drug dimethocaine. Homburg/Saar: University of Saarland.
- ^ a b c d "Dimethocaine - The Drug Classroom". The Drug Classroom. Retrieved 2018-03-16.
- ^ PMID 7635175.
- PMID 23968642.
- ^ PMID 8853299.
- ^ PMID 9698809.
- ISBN 9780124158160.
- PMID 24309420.
- ^ S2CID 15631376.
- ^ TOKYO CHEMICAL INDUSTRY CO., LTD. (2012-09-28). "Material Safety Data Sheet Dimethocaine".
- .
- ^ "Tretton ämnen föreslås klassas som narkotika eller hälsofarlig vara" (in Swedish). Folkhälsomyndigheten. 25 September 2019. Archived from the original on 31 October 2019. Retrieved 11 November 2019.