Amphetamine toxicity

Parathion is super-toxic, amphetamine is extremely toxic, chlordane is very toxic, malathion is moderately toxic, succinic acid is slightly toxic, and finally sulfapyridine is practically nontoxic. 

Especially in earlier decades, many clinicians purposefully administered tricyclics until they produceed toxic reactions. Goodwin and Ebert (1977) advised giving the tricyclics in doses that produce confusion and other signs of toxicity. Amphetamine-like toxic effects were considered a good sign. Wells and Mendelson (1978) observed, In our practice, an adequate trial often constitutes the highest dose that the patient can tolerate. ... 

A little later, he vomited, his breathing became shallow and he eventually stopped breathing. CPR was performed but he was pronounced dead 30 min later. Toxicology revealed MDMA (2.6 mg/mL), MDA (0.1 mg/mL), methamphetamine (0.1 mg/mL) and moclobemide. The cause of death was serotonin toxicity, amphetamine toxicity, pulmonary oedema and cerebral oedema. 

Antipsychotic medications are indicated in the treatment of acute and chronic psychotic disorders. These include schizophrenia, schizoaffective disorder, and manic states occurring as part of a bipolar disorder or schizoaffective disorder. The co-adminstration of antipsychotic medication with antidepressants has also been shown to increase the remission rate of severe depressive episodes that are accompanied by psychotic symptoms. Antipsychotic medications are frequently used in the management of agitation associated with delirium, dementia, and toxic effects of both prescribed medications (e.g. L-dopa used in Parkinson s disease) and illicit dtugs (e.g. cocaine, amphetamines, andPCP). They are also indicated in the management of tics that result from Gilles de la Tourette s syndrome, and widely used to control the motor and behavioural manifestations of Huntington s disease. 

The only evidence on chronic amphetamine administration and heightened aggressiveness derives from the studies, discussed earlier, on group-housed placid laboratory rats or mice. The behavioral validity of these phenomena under near-toxic dosage conditions, however, needs to be resolved. 

The stimulation of locomotor activity by MDMA and the importance of mesolimbic dopamine in this response reflect similarities with the prototype phenylethylamine stimulant, amphetamine. It is important to note that these parameters are frequently associated with rewarding aspects of drugs and drug abuse. Additionally, the behavioral profiles of MDMA and I E share certain characteristics with hallucinogen-Iike agents. This unique mixture of stimulus properties and neurochemical actions may contribute to a dangerous behavioral toxicity and neurotoxic potential for drugs like MDMA. 

RESPONSE Yes, and there is some recent study too that was done by Lyness showing that if the serotonin system is destroyed, toxicity and seh-admirhstration of amphetamines are increased. There is a lot of evidence that some of this interaction does occur at some level, but we don t know where yet. 

Table 2 summarizes results of neurotoxicity studies that have utilized the same regimen of drug injections (twice daily for 4 days) and survival times (2 weeks). In addition, the ability of these drugs to suppress milk intake in rats is also presented. It is clear that ring-substituted amphetamines are more potent in terms of absolute dose required to reduce amine content than is the parent compound amphetamine. With regard to relative potency, METH is toxic to DA and 5-HT neurons at doses that are more than tenfold higher than doses that produce anorexia, whereas fenfluramine,... 

The possibility that an aetive metabolite is involved in the neurotoxic effects of amphetamine analogs reeeives limited discussion in this chapter and has been considered previously, espeeially with />-chloroamphetamine (Miller et al. 1986.) Partly beeause the ehemieal structures of these amphetamines do not suggest ways in whieh they would be toxic to neurons, the... 

I have argued in the past that looking further at amphetamine toxicity in terms of understanding the mechanism by which those neurons die, might be more revealing. That is not to belittle the importance of MPTP as a model of Parkinson s disease. Certainly in terms of effects in the MPTP-treated monkeys, these animals are of unquestioned value. But in terms of the mechanism by which the neurons die, that was the point that I was questioning, whether the MPTP model would mimic as well as the amphetamine model. 

OWENS has prepared antibodies to PCP in goats. When administered to mice the PCP levels in blood rose tenfold as an antibody-bound form that was readily excreted in urine. BROWNE tested the selfadministration by rats of 1,000 compounds related (and not related) to PCP, some of which produced PCP-like effects. One compound that was self-administered prevented the entrance of PCP into brain. BALSTER gave a general review of the effects produced by PCP in laboratory animals and showed that some effects were similar to those produced by amphetamine, some to barbiturates, and some to antipsychotics. This response profile makes PCP a unique drug that stands alone in its complex effects and toxicity. 

Uni 1ke other drugs of abuse, the diagnosis of PCP intoxication is often difficult because of the wide spectrum of clinical findings that occurs with this drug. PCP toxicity sometimes can be mistaken for delirium tremens, acute psychiatric illness, sedative/ hypnotic overdosage, amphetamine intoxication, or sedative/ hypnotic withdrawal syndromes. 

BZ is usually disseminated as an aerosol with the primary route of entry into the body through the respiratory system the secondary route is through the digestive tract. BZ blocks the action of acetylcholine in both the peripheral and central nervous systems. As such, it lessens the degree and extent of the transmission of impulses from one nerve fiber to another through their connecting synaptic junctions. It stimulates the action of noradrenaline (norepinephrine) in the brain, much as do amphetamines and cocaine. Thus, it may induce vivid hallucinations as it sedates the victim. Toxic delirium is very common. 

Many people believe that organic or natural psychedelics such as peyote, magic mushrooms and marijuana are safer or produce better trips than synthetic compounds. This is almost certainly false, since any plant material contains hundreds of compounds, many of which have a definite toxicity, but few of which have psychedelic properties (they tend to make you sick, not stoned). The various impurities or the additives (e.g., amphetamine, belladona, strychnine) sometimes found in synthetic preparations are probably no more toxic than many of the compounds found in the psychedelic plants, and like these compounds, such additives or impurities probably have relatively little effect on the trip. 

It is probably best to avoid p-methoxyamphetamine (PMA) and 2,5-dimethoxy-4-methylamphetamine (STP), the former because it seems to have a high toxicity and the latter because it lasts too long (e.g., 24 hours for a minimum dose). Other 4-alkyl amphetamines also seem to be toxic. A number of apparent fatalities due to MDA have been noted, but the reports usually involve very large amounts, often in combination with other drugs (e.g., 7 g MDA plus barbiturates) and screening for other, more toxic drugs (in particular, PMA) has not been done. 

A series of 1-substituted 3-phenylbenzazepines have been evaluated. It was found that the aminopropyl derivative (6, n = 3 R1 = R2 = Et) counteracted amphetamine toxicity, and that the piperazinyl derivative (6) (n = 2 NR R2 = N(CH2CH2)2 = NCH2CH2OH) gave protection against maximal electroshock seizures (MES) [12]. None of the other derivatives such as the 2-oxo derivatives showed any significant effects on the central nervous or cardiovascular system, nor did any of them exhibit any diuretic or hypo-glycaemic activity [12]. Several similar compounds possess antiarrhythmic and antihypertensive effects this will be mentioned in a later section. 

Despite being in pill form, Ecstasy tablets often contain impurities that can be toxic and cause serious adverse reactions. Such impurities may include other amphetamine derivatives,... 

Toxic psychosis Several monoamine stimulants including cocaine are known to produce a temporary or even a lasting psychotic state after heavy use. Reviews of numerous clinical case reports have shown amphetamine to produce a chronic psychotic state, sometimes persisting for months after cessation. There appears to be a sensitization effect in this regard, because after recovery, psychotic states may recur with minimal use of amphetamine or alcohol. When compared to schizophrenic patients, people with amphetamine-induced psychosis demonstrate fewer negative symptoms (Boutros and Bowers 1996). 

As would be expected, khat overuse produces symptoms similar to those of other monoamine stimulants, such as cocaine or amphetamine, including signs of sympathetic overarousal. In the extreme this can involve a toxic psychosis. Disorders more frequently associated with chronic khat use in males are headaches, anorexia, insomnia, constipation, and respiratory illnesses (Kennedy et al. 1983). Females report higher incidences of acute gastritis, jaundice, bronchitis and hepatic diseases. Also, cathinone has toxic reproductive effects in humans and experimental animals (Islam et al. 1990). It decreases sperm count and motility, and increases the number of abnormal sperm cells. It also decreases plasma testosterone in rats. 

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