Aight broskis, let’s pick up where we left off. Only a limited base of knowledge exists concerning the mechanism of the drugs found in “bath salts”. Mephedrone and MDPV are such drugs. As analogues of cathinone, these drugs modulate the release and uptake of neurotransmitters such as noradrenaline (NA), dopamine (DA) and serotonin (5-HT) with the neuronal networks of the brain. See this previous post for an explanation of the role of neurotransmitters within these networks.
How do these drugs elicit their effects?
Once a signal has been relayed across the synapse between two neurons, the neurotransmitters must be removed from the cleft. It is the dynamic switching on and off of specific neuronal networks that allow for organisms to constantly receive information regarding their surroundings. Therefore, without the ability to clear the cleft of neurotransmitter, whole neural pathways are rendered permanently activated, leading to prolonged stimulation.
This is the role of monoamine transporters, bound to the membrane of the presynaptic knob. These are protein structures devoted to the pumping of neurotransmitters from the extracellular back into the cell to be recycled. These are a key target of cathinone analogues.
The effects of many cathinone analogues on these processes were characterised by Simmler et al. through in vitro experimentation using HEK 293 cells. As it is easy to genetically engineer these cells to express specific proteins, HEK 293 cells have been extensively used in cell biology. In Simmlers experiments, the cells were made to express the monoamine transporters SERT, NET and DAT in their membranes which recycle serotonin, noradrenaline and dopamine respectively. The cells were subsequently treated with the drugs to discover their effect.
It was found that Mephedrone was a non-selective monoamine uptake inhibitor. That is, Mephedrone bound and blocked all the 3 types of monoamine transporter, inhibiting the reuptake of neurotransmitters, prolonging neural stimulation, much like cocaine. It was also witnessed that, much like ecstasy and MDMA, that the drug also stimulated the release of 5-HT into the cleft, increasing the effective concentration of neurotransmitter in the cleft. This leads to the euphoric feelings often described by those who have taken “bath salts”.
Similarly, MDPV readily blocks the recycling of dopamine and noradrenaline by binding with a high affinity to monoamine transporters. Coupled with the fact that the drug is highly permeable across the blood-brain barrier we can see why its effects are so potent.
There was a shocking incident sometime last year in America in which a man who had supposedly taken “bath salts” attacked a man and ravaged his face. That’s how badly these things can jack your brain up. Furthermore, there is no way of knowing what you are buying when dealing with these generically labelled products. I’d recommend keeping yourself well away from “bath salts”, the such like and indeed drugs in general. Dangerous they may be!
That’s enough science. Here’s a short film for those in need of some light entertainment. WARNING: Mature content. Not safe for work.
Stay safe out there comrades,