Risperidone counteracts lethality in an animal model of the serotonin syndrome

Nisijima, Koichi; Yoshino, Tatsuki; Ishiguro, Takeo

doi:10.1007/s002130000397

Cited by 60 publications

(27 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The behavioral and physiological features of this syndrome include hypolocomotion, head twitch, forepaw treading, tremors, hindlimb abduction, flat body posture or hunched back, cyanosis, and hyperthermia. In rodents, 5-HTP induces a serotonin syndrome at dosages of 100-200 mg/ kg (Casal et al, 2000;Nisijima et al, 2000Nisijima et al, , 2001; see Section 4.4.3 for more on serotonin syndrome). This 5-HTP-induced syndrome is potentiated by SSRIs.…”

Section: Factors Affecting 5-hydroxytryptophan Availability For Serotmentioning

confidence: 99%

“…Specifically, in rats, 100 mg/kg of 5-HTP increases rectal temperatures to more than 40 -C. At this dose, rats begin to show abnormal behavior and fever as early as 15 min after the drug injection, and all of the rats die between 75 and 90 min after drug administration (Nisijima et al, 2000(Nisijima et al, , 2001. Hirai et al treated SpragueDawley and Wistar rats (reportedly a rat strain that is most sensitive to 5-HTP) and observed lethal damage in the kidneys.…”

Section: Eosinophilia Myalgia Syndromementioning

confidence: 99%

See 1 more Smart Citation

Serotonin a la carte: Supplementation with the serotonin precursor 5-hydroxytryptophan

Turner

Loftis

Blackwell

2006

Pharmacology & Therapeutics

270

158

View full text Add to dashboard Cite

This paper reviews the preclinical and clinical evidence regarding the use of the dietary supplement 5-hydroxytryptophan (5-HTP) for the treatment of depression. In the absence of supplementation with exogenous 5-HTP, the amount of endogenous 5-HTP available for serotonin synthesis depends on the availability of tryptophan and on the activity of various enzymes, especially tryptophan hydroxylase, indoleamine 2,3-dioxygenase, and tryptophan 2,3-dioxygenase (TDO). Factors affecting each of these are reviewed. The amount of 5-HTP reaching the central nervous system (CNS) is affected by the extent to which 5-HTP is converted to serotonin in the periphery. This conversion is controlled by the enzyme amino acid decarboxylase, which, in the periphery, can be blocked by peripheral decarboxylase inhibitors (PDIs) such as carbidopa. Preclinical and clinical evidence for the efficacy of 5-HTP for depression is reviewed, with emphasis on double-blind, placebo-controlled (DB-PC) trials. Safety issues with 5-HTP are also reviewed, with emphasis on eosinophilia myalgia syndrome (EMS) and serotonin syndrome. D

show abstract

Section: Factors Affecting 5-hydroxytryptophan Availability For Serotmentioning

confidence: 99%

Section: Eosinophilia Myalgia Syndromementioning

confidence: 99%

Serotonin a la carte: Supplementation with the serotonin precursor 5-hydroxytryptophan

Turner

Loftis

Blackwell

2006

Pharmacology & Therapeutics

270

158

View full text Add to dashboard Cite

show abstract

“…Under laboratory conditions, a 5-HT toxidrome was usually induced in rats by injection of monoamine oxidase (MAO) inhibitors combined with 5-HT precursors (Grahame-Smith, 1971a;Modigh and Svensson, 1972;Jacobs and Klemfuss, 1975;Abdel-Fattah et al, 1995;Nisijima et al, 2000). The behavioral signs of the toxidrome are many, commonly including somatic (forepaw treading, flat body, hind limb abduction, head shakes, tremor, Straub tail) and autonomic responses (cyanosis, diarrhea, salivation, hyperthermia).…”

Section: Introductionmentioning

confidence: 99%

Characterization of serotonin-toxicity syndrome (toxidrome) elicited by 5-hydroxy-l-tryptophan in clorgyline-pretreated rats

Ma¹,

Zhang²,

Jenney³

et al. 2008

European Journal of Pharmacology

View full text Add to dashboard Cite

Patients are at high risk of developing serotonin-toxicity syndrome (toxidrome) when they take multiple serotonergic drugs, particularly co-administered with monoamine oxidase inhibitors or 5-hydroxytryptamine (5-HT) reuptake blockers. The toxidrome can vary from mild to severe. The primary goal of the present study was to understand the relationship between behavioral signs and degrees of toxidrome induced by 5-hydroxy-L-tryptophan (5-HTP) in clorgylinized rats. The severity was obtained by scoring behavioral signs including head shakes, penile erection, forepaw treading, hind limb abduction, Straub tail and tremor. It was found that 5-HTP produced a dosedependent increase in degrees of the toxidrome. Furthermore, correlation between the toxidrome and changes in body-core temperature (claudqcT cor ) was determined. There was hypothermia in the mild toxidrome (claudqcT cor < −1 °C), high hyperthermia in the severe toxidrome (claudqcT cor > +2 °C) and a small change in T cor in the moderate toxidrome (−1 °C < claudqcT cor < +2 °C). Thus, claudqcT cor in response to drugs can be used to estimate the severity of the toxidrome. The second attempt was to identify the receptors mediating those changes. 5-HT 1A receptors were involved in the hypothermic response while 5-HT 2A and NMDA receptors mediated head shakes, hyperthermia, forepaw treading and Straub tail. Lastly, antidotal effect of cyproheptadine and (+)-MK-801 was examined. Both drugs blocked hyperthermia and death. However, the effects on mortality became poor when the antidotes were injected 60 min after high hyperthermia had been induced. These findings demonstrate the importance of the time frame using antidotes in the treatment of the 5-HT toxidrome.

show abstract

“…There is increasing use of 5-HT 2A receptor antagonists, such as cyproheptadine and chlorpromazine, which appear to be effective based on clinical experience [24,27] and animal studies [28,29]. However, all six severe cases in this series required intubation, sedation and most importantly muscle paralysis.…”

Section: Clinical Effects Of Moclobemide Poisoningmentioning

confidence: 89%

Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity

Hackett

Dawson

Whyte

et al. 2003

Brit J Clinical Pharma

View full text Add to dashboard Cite

Aims To investigate the spectrum of toxicity of moclobemide overdose, the occurrence of serotonin toxicity, and to estimate toxicokinetic parameters. Methods All moclobemide overdoses presenting over a 10-year period to the Hunter Area Toxicology Service were reviewed. Clinical features, complications, length of stay (LOS) and intensive care (ICU) admission rate were extracted from a standardized, prospectively collected database. Comparisons were made between moclobemide alone and moclobemide with a serotonergic coingestant poisoning. Serotonin toxicity was defined by a combination of Sternbach's criteria and a clinical toxicologist's diagnosis. In five patients serial moclobemide concentrations were measured. Time to maximal plasma concentration ( T max ), peak plasma concentration ( C max ) and terminal elimination half-lives were estimated. Results Of 106 included patients, 33 ingested moclobemide alone, 21 ingested moclobemide with another serotonergic agent (in some cases in therapeutic doses) and 52 ingested moclobemide with a nonserotonergic agent. Eleven (55%) of 21 patients coingesting a serotonergic drug developed serotonin toxicity, which was significantly more than one (3%) of 33 moclobemide-alone overdoses (odds ratio 35, 95% confidence inteval 4, 307; P < 0.0001). In six of these 21 cases severe serotonin toxicity developed with temperature > 38.5 ∞ C and muscle rigidity requiring intubation and paralysis. The 21 patients had a significantly increased LOS (34 h) compared with moclobemide alone overdoses (12 h) ( P < 0.0001) and a significantly increased ICU admission rate of 57% vs. 3% ( P < 0.0001). Time to peak plasma concentration was delayed in two patients where prepeak samples were obtained. C max increased slightly with dose, but all three patients ingesting ≥ 6 g vomited or had charcoal. The mean elimination half-life of moclobemide in the five patients in whom serial moclobemide concentrations were measured was 6.3 h and elimination was first order in all cases. There was no evidence of a dose-dependent increase in half-life. Conclusions The effects of moclobemide alone in overdose are minor, even with massive ingestions. However, moclobemide overdose in combination with a serotonergic agent (even in normal therapeutic doses) can cause severe serotonin toxicity. The elimination half-life is prolonged by two to four times in overdose, compared with that found in healthy volunteers given therapeutic doses. This may be a result of wide interindividual variation in overall elimination, also seen with therapeutic doses, but appears not to be due to saturation of normal elimination pathways.

show abstract

Risperidone counteracts lethality in an animal model of the serotonin syndrome

Abstract: These results suggest that strong 5-HT2A antagonists such as risperidone, but not dopamine D2 antagonists, counteract lethality due to 5-HT syndrome, and that not only does enhancement of 5-HT activity occur in the 5-HT syndrome, but NA activity also increases.

Cited by 60 publications

References 25 publications

Serotonin a la carte: Supplementation with the serotonin precursor 5-hydroxytryptophan

Serotonin a la carte: Supplementation with the serotonin precursor 5-hydroxytryptophan

Characterization of serotonin-toxicity syndrome (toxidrome) elicited by 5-hydroxy-l-tryptophan in clorgyline-pretreated rats

Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity

Contact Info

Product

Resources

About