Algemene Informatie: Ketamine

Pharmacologically, ketamine is classified as an NMDA receptor antagonist, but it also acts at numerous other sites (including opioid receptors and monoamine transporters).

Several studies indicated that opioid receptors are also involved in the pharmacological effects of ketamine (Freo, 2002), and that the analgesic effect of ketamine may largely be attributed to the activation of these central and spinal receptors (Crisp et al 1991).

Furthermore new developments show strong interactions between the opioid and the NMDA system in the brain of animals. In contrast to earlier findings new results point to NMDA receptors and not sigma-receptors as having a role in the morphine withdrawal response (Brent et al, 1993). Gonzalez et al (1997) has shown that competitive and non-competitive NMDA receptor antagonists prevent morphine tolerance and decrease the development of physical dependence on this opiate in mice. The study of Ji et al (2004) indicates that ketamine has the ability to suppress morphine withdrawal syndrome in experimental settings without motor interference. The Nucleus Accumbens is mentioned as the site of action.

Some effects of ketamine may be due to its actions on catecholamine systems, notably an enhancement of dopamine activity (White and Ryan, 1996; Vollenweider et al., 2000; Smith et al., 1998). A series of experiments by Hancock and Stamford (1999) on the effects of ketamine on uptake and efflux of dopamine in the rat nucleus accumbens (NAc) led the authors to conclude that ketamine increases NAc dopamine efflux not by block of dopamine uptake, autoreceptors or NMDA receptors, but by mobilization of the dopamine storage pool to releasable sites. In the rat, it has been shown that repeated ketamine administration diminished the initial five-fold increase in dopamine release in the prefrontal cortex, whereas the increase in extracellular 5-hydroxyindole acetic acid (a serotonin metabolite) levels is enhanced. This suggests, that the balance between dopamine and serotonin neurotransmission in the prefrontal cortex is altered after repeated exposure to ketamine (Lindefors et al., 1997). The dopaminergic effects may be of relevance for the euphorigenic, addictive and psychotomimetic properties of ketamine.

Other neuropharmacological actions are an agonistic effect on α- and β-adrenergic receptors, an antagonistic effect at muscarinic receptors of the CNS, and an agonistic effect at the σ-receptor (Bergman, 1999). The principal metabolite, norketamine, is pharmacologically active. Its binding affinity to the NMDA-receptor and anaesthetic properties are approximately one third of the parent compound contributing significantly to the analgesic effect of ketamine (Shimoyama et al.,
1999).

PET molecular imaging of the brain reveals that ketamine may act as an antidepressant by boosting serotonin activity in brain areas involved in motivation.

To understand the effects of ketamine on the serotonergic system in the brain, Dr Hajime Yamanaka and Dr Hirotaka Onoe, who has pioneered PET imaging on conscious non-human primates, together with an international team, performed a PET study on rhesus monkeys. The procedure was painless for the monkeys, and PET scans are performed regularly on humans to diagnose health conditions.

The team performed PET imaging studies on four rhesus monkeys with two tracer molecules related to serotonin (5-HT) that bind highly selectively to the serotonin 1B receptor 5-HT1B and the serotonin transporter SERT.

From the analysis of the 3 dimensional images generated by the PET scans, the researchers could infer that ketamine induces an increase in the binding of serotonin to its receptor 5-HT1B in the nucleus accumbens and the ventral pallidum, but a decrease in binding to its transporter SERT in these brain regions. The nucleus accumbens and the ventral pallidum are brain regions associated with motivation and both have been shown to be involved in depression.

In addition, the researchers demonstrate that treatment with NBQX, a drug known to block the anti-depressive effect of ketamine in rodents by selectively blocking the glutamate AMPA receptor, cancels the action of ketamine on 5-HT1B but not on SERT binding.

Taken together, these findings indicate that ketamine may act as an antidepressant by increasing the expression of postsynaptic 5-HT1B receptors, and that this process is mediated by the glutamate AMPA receptor.

Shortage of ketamine (Ketalar®) injection (all strengths)
Source: London and South East Regional Medicines Information Service
Date published: 29/05/2014 10:04

Pfizer, as the sole licensed supplier, is currently experiencing supply problems of Ketalar 10mg/ml, 50mg/ml and 100mg/ml presentations in the UK. The 10mg/ml and 100 mg/ml strengths are anticipated to be out of stock until March 2015. Current stock of the 50 mg/ml strength is anticipated to be exhausted during May 2014. Pfizer are however working to ensure that further supplies of this strength are made available as soon as possible.

BigY schreef:Ik ben inmiddels al voor 2k euro opgelicht. De meest bizarre meuk heb ik gekregen waaronder ket die echt perfect eruit ziet en zelfs rood uitslaat in de keta test. Maar het doet totaal niets....niet alleen bij mij, maar ook bij anderen die het hebben geprobeerd.

Ik baal er enorm van want ik verlies zo ook het vertrouwen van sellers.

Maurits schreef:

BigY schreef:Ik ben inmiddels al voor 2k euro opgelicht. De meest bizarre meuk heb ik gekregen waaronder ket die echt perfect eruit ziet en zelfs rood uitslaat in de keta test. Maar het doet totaal niets....niet alleen bij mij, maar ook bij anderen die het hebben geprobeerd.

Ik baal er enorm van want ik verlies zo ook het vertrouwen van sellers.

EUR 2000?

Eko schreef:Iets dat als ketamine wordt verkocht, maar geen effect heeft, zelf meegemaakt en de laatste tijd al meer gelezen hier, iemand een idee wat dit is, en of we een waarschuwingsbericht moeten maken, het idee dat ik een onbekende stof in mn neus snoof is niet bepaald aangenaam.

BigY schreef:En huppakee, weer 200USD weg. Net wat binnen gekregen en precies hetzelfde verhaal. Keta tester zegt nep, en idd....150mg nasaal doet niets. Wederom ziet het er perfect uit.

Ik hou er maar mee op....