Carisoprodol Intoxications and Serotonergic Features

Abstract

CASE REPORTThe symptoms and signs of carisoprodol intoxications do not resemble those caused by its metabolite meprobamate. Meprobamate most probably produces its effects through the GABAergic neurotransmitter system. The signs and symptoms of carisoprodol intoxications, however, are not easily explained by interaction with this neurotransmitter system. In the present study, four cases of carisoprodol intoxications are presented with emphasis on the presence of serotonergic signs and symptoms. All four cases fulfilled three different sets of criteria for the diagnosis of serotonin syndrome. These findings could indicate that an increased serotonin level in the central nervous system could explain some of the symptoms and signs of carisoprodol intoxications. This may have implications for the clinical evaluation and treatment of such intoxications. Since few laboratories routinely screen for carisoprodol it is important to keep this drug in mind when encountering intoxications displaying serotonergic symptoms.

Carisoprodol intoxications: a retrospective study of forensic autopsy material from 1992–2003

“…Secondly, a death from the barbiturate-like meprobamate would be expected to be more protracted, although it seems that carisoprodol has a mechanism that leads to a more sudden death. Previous studies have reported symptoms after carisoprodol intoxication resembling those of the serotonin syndrome unlike the CNS-depressing symptoms produced by meprobamate [11][12][13][14]. In theory, the combination of carisoprodol and SSRIs could be especially dangerous, and the frequent finding of SSRIs (n=22) in the present study, as well as the tendency of lower concentrations of carisoprodol in these cases, might strengthen this assumption.…”

“…The mechanism of deaths from carisoprodol overdose is not known in detail. Despite genetic polymorphism [33] and possible saturation of enzymes after ingestion of large doses [11], the ratio between carisoprodol and meprobamate in group A, especially group A1, in the present study indicated relatively recent ingestion of carisoprodol [1,32,33] compared to group A3 and the reference groups B and C.…”

“…Meprobamate probably has a barbiturate-like mode of action [15], whereas carisoprodol's mode of action is not known. The symptoms of carisoprodol intoxication indicate that it might act differently from meprobamate, and we have suggested earlier the possible involvement of the serotonin system in carisoprodol toxicity [11]. Carisoprodol is a potentially lethal drug, but there are inconsistencies in the literature with regard to which concentration levels are toxic.…”

“…Case reports on carisoprodol abuse are numerous [7][8][9][10], and there are also several reports on carisoprodol intoxication [11][12][13][14], but the extent and possible seriousness of this problem is not known in detail. Meprobamate probably has a barbiturate-like mode of action [15], whereas carisoprodol's mode of action is not known.…”

Characterizing the subjective and psychomotor effects of carisoprodol in healthy volunteers

“…However, signs of carisoprodol toxicity from an overdose occur before it is significantly dealkylated to meprobamate, and the signs do not resemble classic signs of meprobamate toxicity (Roth et al, 1998; Bramness et al, 2004). In fact, a recent case report suggested that the signs of carisoprodol toxicity resemble central serotonin syndrome (Bramness et al, 2005a). Whether serotonin plays a role in mediating the effects of carisoprodol remains to be determined, but there is in vitro and in vivo evidence that carisoprodol acts via the GABAergic system, independent of meprobamate.…”