Several studies have tested the weak base hypothesis by comparing effects on vesicular pH and catecholamine redistribution.
#Developer amphetamine free
Weak base compounds that are sufficiently membrane-permeable to enter secretory vesicles bind free protons, alkalinize the existing vesicular acidic pH gradient and thus decrease the energy that drives the accumulation of neurotransmitters (Markov et al., 2008 Sulzer and Rayport, 1990). Secretory vesicles are acidic vesicles maintain a pH of 5.0 – 5.7, depending on conditions (Markov et al., 2008) that provide the energy to accumulate monoamine transmitters. The acidic pH gradient in secretory vesicles provides the energy to accumulate neurotransmitters against their concentration gradient. Thus, they can be protonated in acidic organelles including catecholamine vesicles (Sulzer and Rayport, 1990): once charged, they become less membrane-permeable and accumulate in the acidic structure. There are two main hypotheses as to how vesicular content in released into the cytoplasm.Īll sympathomimetic compounds are weak bases with amine moieties that are capable of accepting protons with pKs in the range of ~ 8 to 10. Vesicular Neurotransmitter Release by Amphetamines (MDMA, Amphetamine, Meth.) there is a higher concentration of free monoamines inside the terminal), which, in turn, causes their release into the synaptic cleft by reverse transport, mediated by the monoamine transporters mentioned above (Leviel, 2001) (Fig. Due to the high concentrations of cytoplasmic neurotransmitters, there is a shift in the gradient (i.e.
Once they enter the synaptic terminal, amphetamines are capable of massively releasing neurotransmitters, which are contained in vesicles. This high affinity for monoamine transporters is explained by the high homology between amphetamines and catecholamines, such as dopamine or norepinephrine. Nonetheless, the main psychostimulant and reinforcing effects of amphetamines are generally attributed to the release of dopamine (Gulley and Zahniser, 2003 Kuczenski et al., 1995 Sulzer et al., 2005).Īmphetamines enter the synaptic terminal through monoamine transporters, mainly the dopamine, norepinephrine and serotonin transporters (abbreviated DAT, NET and SERT, respectively), where they act as substrates (Liang and Rutledge, 1982 Zaczek et al., 1991). Depending on their specific structure, these compounds can evoke an increase in dopamine, norepinephrine and serotonin, at different ratios and to different degrees. They increase extracellular neurotransmission by promoting the release of neurotransmitters found in presynaptic vesicles. Synaptic terminals are endowed with vesicles that store reserves of neurotransmitters, which, in physiological conditions, are released through exocytosis into the synaptic cleft at a controlled rate.Īmphetamines are, with few exceptions, psychostimulants of the releaser type. Generic mechanism of action of amphetamines: Amphetamine, Methamphetamine and methylenedioxymethamphetamine (MDMA) are the most popular substances of this group among users. Amphetamines, as suggested by their generic name (Alpha- MethylPHenEThylAMINE), are comprised of a phenyl ring connected to an amino group by a two-carbon side-chain with a methyl group on carbon-1 of the side chain (Fig.
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