Hyperthermic effect

Brimblecombe, R. W. (1967) Hyperthermic effects of some tryptamine derivatives in relation to their behavioral activity. Int. J. Neuropharmacoi, 6 423-429. 

Behavioral and emotional effects In animal studies, ginseng does not prolong pentobarbital-induced sleep, nor does it affect spontaneous locomotion (Mitra et al. 1996). It does potentiate amphetamine-induced locomotion, but it reduces the stereotypy and lethality caused by amphetamine. Ginseng has analgesic effects, which are discussed at greater length in chapter 8. Catalepsy induced by haloperidol is potentiated by ginseng, while the hyperthermic effect of 5-HTP is attenuated. No antiseizure effects have been observed. 

Unfortunately, children, especially infants, are very sensitive to the hyperthermic effects of atropine. Although accidental administration of over 400 mg has been followed by recovery, deaths have followed doses as small as 2 mg. Therefore, atropine should be considered a highly dangerous drug when overdose occurs in infants or children. 

Abdel-Fattah, A., Matsumoto, K., El-Hady, K., and Watanabe, H., 5-HT1A and 5-HT2 receptors mediate hypo- and hyperthermic effects of tryptophan in pargyline-pretreated rats, Pharmacology Biochemistry and Behavior, Vol. 52, No. 2, 1995, pp. 379-384. 

The effect of nonfatal injuries such as a 2-hour period of bilateral hind-limb ischemia or a full-thickness scald of 20% of skin surface on the LDso of DNOC and its hyperthermic effect were evaluated in male rats (Stoner 1969). The intraperitoneal LDs° of DNOC was significantly (p<0.001) reduced from 24.8 to 26.2 mg/kg to 14 mg/kg DNOC when DNOC was given 1.5- 24 hours after either type of nonfatal injury. The authors concluded that the toxicity of DNOC was increased by previous trauma. These investigators proposed that this interaction was associated with sequential blocking of the tricarboxylic acid cycle with inhibition of citrate synthetase reaction during the early part of the response to the injury. Because DNOC acts as an uncoupler of oxidative phosphorylation, less ATP is produced. Therefore, the effects of trauma will be enhanced by an uncoupling agent such as DNOC. 

In both cases, the blood metamfetamine concentration was less than the lethal concentration of 4.5 pg/ml. Morphine concentrations were higher than the non-toxic concentration of 0.3 pg/ml. It is unlikely that morphine was the cause of death, because it would have caused hypothermia instead of hyperthermia. It is more likely that morphine interacted with metamfetamine, increasing the hyperthermic effect that is typical of metamfetamine overdose. This would explain why hyperthermia caused death, despite a non-lethal blood concentration of metamfetamine. 

These reports show that hyponatremia due to ecstasy occurs primarily due to inappropriate secretion of antidiuretic hormone and relative excess liquid intake, usually in the setting of a warm environment and possible hyperthermic effects of ecstasy. Excess water ingestion should be discouraged in ecstasy users. 

The authors reviewed the possible explanations, which included excess water ingestion, SIADH, and the serotonin syndrome. While many ecstasy users drink water to counter its hyperthermic effects, others do it because of health advice given at such parties to prevent toxic effects. However, death can occur due to water intoxication, albeit infrequently. 

The authors of the last report postulated a hyperthermic effect of ecstasy on the hver or a direct toxic effect of ecstasy on hepatocytes as possible mechanisms. 

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