What is methamphetamine ?
Methamphetamine, or crystal meth is a highly addictive amphetamine and belongs to the phenethylamine family. It is a lipophilic molecule with a potent action on the central nervous system. It may be at a slightly acidic pH, also be present in the protonated form.
The increased lipophilicity works methamphetamine compared to ordinary amphetamine stronger and therefore has a stronger toxic effect.
Applications
Medical applications
There are several medical applications for this product. Methamphetamine is sold under the name Desoxyn by the Danish company Lundbeck pharmaceutical for the treatment of narcolepsy, obesity and ADHD. It is used as a slimming agent (because the appetite is suppressed) and extreme forms of ADHD and ADD. Methamphetamine is usually in its crystalline form as methamphetamine hydrochloride ingested.
Other applications
Methamphetamine is a popular hard drug. It is also used by people who want to do well under pressure or need to perform like athletes, students or pilots.
Synthesis
There are basically two different synthetic mechanisms. The reduction of ephedrine and the condensation of phenylacetone.
Reduction
The reduction of ephedrine was first developed synthesis mechanism and was developed in 1894 by the Japanese chemist Nagayoshi Nagai.
Condensation
The condensation of phenylacetone with methylamine was developed in 1919 by Akira Ogata. He obtained for the first time methamphetamine in a crystalline pure form. In 1921 he applied for a patent for this synthesis.
Chemical properties
Methamphetamine is a colorless volatile lipophilic substance, which is therefore well able to penetrate the blood-brain barrier and to be stored in adipose tissue. Methamphetamine, however, also can be used as water-soluble ammonium ion are present. The amine nitrogen has a pKa = 9.9 and will thus in mildly acidic solutions are present are protonated and therefore also easy to accumulate in acidic cell compartments such as mitochondria, or neurotransmitter vesicles.
Effects of methamphetamine
Methamphetamine effects on nervous system
Methamphetamine is by its chemical similarities with catecholamines a substrate retention mechanisms. It is actively transported by dopamine-plasma membrane transporters and vesicular monoamine transporters within the cell. These are transporter proteins, which are normally suitable for the re-uptake of released dopamine and, inter alia, determine the concentration of dopamine in the synaptic cleft. The affinity of methamphetamine to the transporter proteins is 10 times higher than for amphetamines. The passive transport mechanism is diffusion through the membrane.
Inside the cell goes methamphetamine further organelles, including mitochondria and vesicles in. Here, it increases the pH and changes of enzyme activities. Of particular interest here is the reduction of the MAO-activity in the mitochondria and inhibition of catecholopslag in vesicles. As a result, the neurotransmitter concentration is increased in the cell. The neurotransmitter binds to the inward-pointing side of the transporter protein and is transported in the synaptic cleft. The catecholamine binds to the postsynaptic receptors and exerts its function.
Methamphetamine effects on the body
The increased release of catecholamines, so called fight-flight response generated. Typical effects are:
- Increase in heart rate
- Increase in blood pressure
- Narrowing of the arteries
- Increased sweating
- Dilation of the respiratory tract
- Increasing pupils
Overdose
Methamphetamine users develop very quickly a large tolerance. Addicts usually take a 5 to 6 times higher dose than the LD50 for a person who uses for the first time. This may cause two serious situations where death is a possible consequence. First abstinent users need the same dose previously in a tolerant state was normal to. Because they have such a high dose can be lethal lost their tolerance. Furthermore, it is common for new users administer the same dose as experienced users. Death occurs by uncontrollable hyperthermia, seizures, hypoxia and cardiovascular complications.
Psychopathology of withdrawal
When methamphetamine addicts in withdrawal anergy (absence of response) with dysphoria, and impairment observed on mental energy. These symptoms are more severe than cocaine and may persist for months. Also psychosis often seen and a high susceptibility to paranoia that can take years. This probably is not related to the neurotoxicity as well as withdrawal from cocaine, barely a neurotoxic substance, is observed.
Methamphetamine effects in the brains
Chronic abuse of methamphetamine has a very strong effect on the metabolism in the brains, especially in the parietal cortex, thalamus and striatum. In the parietal cortex increased metabolism is fixed, while in the thalamus and striatum to observe is the opposite. This was also confirmed in experiments in which rats chronically exposed to methamphetamine. The neurotransmitter dopamine plays an important role. Meth Amphetamine has a neurotoxic effect on cells of the middle brains, causing the release of dopamine in the striatum is decreased and therefore its metabolism. Because the thalamus receives most of dopamine from the striatum, the metabolism is also reduced in the thalamus, which ultimately leads to an irreversible deterioration of the fine motor skills. Even after three years of abstinence is the dopamine binding in the caudate nucleus and the putamen reduced. However, the reason for this is not completely known yet. It could be a reflection of neuroadaptie or neurotoxicity. Furthermore, would the consumption pattern for the difference may be responsible. The increased metabolism in the parietal cortex has not yet been fully elucidated, however, research shows that gliosis (an increased number of glial cells in a damaged part of the central nervous system) may be responsible to make.
Cellular mechanisms of toxicity
There are two models of acute and chronic toxicity. Acute toxicity is simulated in animals with administration of about 4-5 mg / kg. One suspects that is oxidized in the cytoplasm in acute exposure to high concentrations of methamphetamine dopamine. As a result, the dopamine loses its effect. Furthermore, the mitochondrion opens pores through which calcium exits and cell death occurs.
Independent of the way how methamphetamine enters the cell, the neurotoxicity of the production of reagents is species-dependent. When methamphetamine enters the cell and dopamine move freely, it is oxidized (with MAO or auto-oxidation). The result; reactive oxygen species through H2O and NO with necrotic cell death. If methamphetamine in the cell mitochondria and diffuses (possibly due to its lipophilicity) it changes there the electrochemical gradient. It is therefore possible that methamphetamine not only through the production of radicals, but also kills the neurons by mitochondria-dependent induction of the apoptotic cascade.