Norepinephrine methamphetamine

Levonordefrine Mephentermine Metaramino1 Methamphetamine A-Norepinephrine Phenylephrine... 

Kuczenski, R., Segal, D.S., Cho, A.K., Melega, W. Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine. J. Neurosci. 15 1308, 1995. 

In the brain, methamphetamine causes massive amounts of the neurotransmitters dopamine, norepinephrine, and serotonin to be released from neurons in the brain, particularly in the limbic system and frontal cortex. Scientists believe the increased dopamine release in these brain regions is responsible for methamphetamine s ability to keep people awake, alert, energetic, active, and possibly addicted. Methamphetamine acts on a variety of brain regions to produce a number of different effects (Table 2.1). 

Antidepressant Some animal models show antidepressant effects of lobelia extract (Subarnas et al. 1992). Similar to imipramine and mianserin, beta-amyrin palmitate shows antidepressant-like effects in the forced-swimming test (Subarnas et al. 1993a). Whereas mianserin and beta-amyrin palmitate reduce locomotor activity induced by methamphetamine, imipramine increases it. It potentiates sodium pentobarbital-induced sleep more potently than imipramine, but less than mianserin. Collectively, the effects of beta-amyrin palmitate in behavioral and physiological assays suggests it may work in a manner more similar to mianserin than imipramine. However, the mechanism of antidepressant-like effects of lobelia is uncertain. It may be through the beta-amyrin palmitate s ability to release norepinephrine (Subarnas et al. 1993b). An antidepressant effect of lobelia has not been established in humans. 

The popular psychostimulant, me-thylenedioxy-methamphetamine (MDMA, ecstasy ) acutely increases neuronal dopamine and norepinephrine release and causes a delayed and selective degeneration of forebrain 5-HT nerve terminals. 

Each neuron has specific synthetic machinery that enables it to both synthesize and eliminate a specific neurotransmitter. For example, neurons of the sympathetic nervous system employ norepinephrine and epinephrine as their transmitters. Other neurons, particularly in the central nervous system, employ dopamine as their transmitter. Dopamine is a particularly important transmitter for a variety of neuronal functions. Its loss is associated with Parkinson disease, and it is a critical agent in the mediation of pleasure and reward processes. Dopamine, due to its association with pleasurable sensations, is widely implicated in the actions of a number of drugs of abuse, including cocaine, opiates, and methamphetamines. 

The composition of the six controlled substance analogs listed above often stimulate the same areas of the brain, but are chemically quite distinct from one another. MDMA (3, 4-methylenedioxymethampheta-mine) is a complex drug that makes simple classification difficult. Its chemical structure is related both to the stimulant methamphetamine and the hallucinogen mescaline. Methamphetamine bears a close resemblance to two powerful chemicals in the body, dopamine and norepinephrine, which regulate mood, memory, and movement. 

Methamphetamine (MAP) is a psychostimulant that induces enhanced arousal and euphoria acutely, and psychosis and addiction chronically. MAP enters the terminals/neuron via the monoamine transporters (dopamine transporter DAT, serotonin transporter SERT, or norepinephrine transporter NET), displaces... 

Although cocaine can function as a local anesthetic, most of its actions relate to a second mechanism. Cocaine increases synaptic concentrations of catecholamines (i.e., dopamine and norepinephrine) in the brain by blocking their reuptake mechanisms. Normally, when these transmitters are released from nerve terminals, they are rapidly removed from the synaptic cleft by specific energy-dependent transporter proteins that carry them back into the terminal. By blocking these transporter systems, cocaine prolongs the time the catecholamines remain in the synapse and intensifies their actions. This increase in dopamine concentration in the CNS appears to be the basis for the various euphoric and related changes that occur in people who use cocaine. A similar mechanism has been suggested for methamphetamine. 

Figure 2.10 Amphetamine 30, methamphetamine 31, and methylenedioxymethamphetamine 32 (MDMA, ecstasy, XTC) are lipophilic compounds with good oral bioavailability they easily cross the blood-brain barrier to exert central nervous system effects. Dopamine 33, norepinephrine (noradrenalin) 34, and epinephrine (adrenaline) 35 are polar phenethylamines they have poor oral efficacy and do not pass the blood-brain barrier, producing only peripheral effects after intravenous application. Ephedrine 36 has intermediate lipophilicity besides its peripheral effects it also acts as a central stimulant. Although L-dopa 37 is even more polar than dopamine 33, it is orally active and crosses the blood-brain barrier by active transport mediated by the amino acid transporter.

Ephedrine and pseudoephedrine share properties with cocaine and with the amphetamines because they (1) stimulate (3-receptors directly, and (2) also cause the increased release of norepinephrine. Chronic exposure to abnormally high levels of circulating catecholamines can damage the heart. This is certainly the case with cocaine and methamphetamine (116,117), but ephedrine-related cardiomyopathy is an extremely rare occurrence, occurring only in individuals who take massive amounts of drug for prolonged periods of time. Only two papers have ever been published on the subject (118,119). 

Pharmacology. In order to assess the importance of conformational preferences in the action of amphetamine at the adrenergic nerve endings, the effect of the amphetamine and methamphetamine analogs (NH-X,-NH-N, NM-X and NM-N) on the uptake and release of JH-norepinephrine (NE) and H-dopamine (DA) in chopped tissues from various regions of rat brain was examined. NH-X and NM-X were nearly as potent as amphetamine in the inhibition of uptake of 3H-NE into chopped cortex... 

Ricaurte and colleagues (1985) demonstrated that an analog of amphetamine, 3,4-methylenedioxyamphetamine (MDA), is neurotoxic to monoamine systems. They observed that neostriatal and hippocampal 5-HT and 5-HIAA contents were depressed after MDA administration and that hippocampal norepinephrine (NE) content was also compromised. In comparing the effects of methylenedioxymethamphetamine (MDMA) and methamphetamine, it was observed (Stone et al. 1986, 1987) that while methamphetamine decreased both TH and TPH activity, MDMA depressed only TPH activity without altering the DA-synthesizing enzyme. Although MDMA releases DA (Yamamoto and Spanos... 

---