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| Other names | DMC, larocaine |
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| Formula | C16H26N2O2 |
| Molar mass | 278.396 g·mol−1 |
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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 asDMC orlarocaine, is a compound with a stimulatory effect. This effect resembles that ofcocaine, 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 theEuropean Monitoring Centre for Drugs and Drug Addiction (EMCDDA) under the category "synthetic cocaine derivatives".[1] The structure of dimethocaine, being a4-aminobenzoic acid ester, resembles that ofprocaine. It is found as a white powder at room temperature.[2]
When a product sold online in the UK in June 2010, advertised as dimethocaine was tested, it was found to be a mixture ofcaffeine andlidocaine,[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]
Dimethocaine was originally synthesized by theHoffmann-La Roche company in 1930. It was sold under the market name larocaine. During the 1930s dimethocaine gained popularity in the US as a local anesthetic. Just like cocaine and procaine, it was used duringsurgery, primarily indentistry,ophthalmology andotolaryngology. However, in the 1940s, it was removed from the market because of its psychoactive effects and risk of addiction. Nowadays dimethocaine is abused for these psychoactive effects. It is sold as a cocaine surrogate to circumvent legislation issues.[1][5][6]
Dimethocaine and structurally related local anesthetics such as cocaine and procaine inhibit the uptake ofdopamine (DA) by blockingdopamine transporters (DAT).[7] The dopamine transporter controls the dynamics of theneurotransmitter 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 ofCFT, a different dopamine uptake inhibitor.[7] These inhibitory properties are responsible for the stimulatory effects of dimethocaine on thecentral nervous system.[5] Bothin vivo andin 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 thenucleus accumbens, a region in thebasal 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 toantinociceptive 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]
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]
The exact metabolic pathways of dimethocaine have not been researched, but the different metabolites have been examined inWistar 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 mainphase I reactions areester hydrolysis,deethylation,hydroxylation of the aromatic system, or a combination of these three.[1] The mainphase II reactions areN-acetylation,glucuronidation and a combination of both.[5][1] Differentcytochrome P450isozymes are involved in the initial steps of human metabolism. The N-acetylation is catalyzed by theNAT2 isozyme.[12]
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 withrhesus 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 administeredintravenously or nasally, because ingestion would lead to rapidhydrolyzation.[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.
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.
For mice, the dose at which acute toxicity occurs for intravenous administration is 40 mg/kg and forsubcutaneous injection (injection in the layer of skin directly below thedermis andepidermis) this is 380 mg/kg.[14] The lethal dose of dimethocaine for a mouse is 0.3 g per kilogram body weight.[15]
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 theelevated plus-maze test in mice.[10]
Sweden's public health agency suggested classifying Dimethocaine as a hazardous substance, on September 25, 2019.[16]
