Carisoprodol: reproductive assessment by continuous breeding in Swiss mice.

Carisoprodol (CARI), a commonly prescribed neuromuscular relaxant, was evaluated for reproductive toxicity in Swiss CD-1 mice using the Reproductive Assessment by Continuous Breeding (RACB) protocol. Male and female mice were given CARI in corn oil suspension by daily gavage at doses of 0, 300, 750, and 1200 mg/kg body wt/day. Clinical signs of general toxicity in F0 animals included sedation, primarily in the high-dose group during the first week of exposure, and reduced body weight in high-dose females. CARI administration for 14 weeks did not affect the ability of the F0 animals to produce litters. However, decreases in proportion of pups born alive (4%) and absolute (5%) and adjusted live pup weight (7%) were observed at 1200 mg/kg CARI when compared to controls. In a crossover mating trial to determine the affected sex, there were no significant differences in the measured reproductive parameters. CARI at the high dose increased the proportion of time spent in proestrus and estrus, but cycle length was unaffected. At F0 necropsy (Week 27 of treatment), all sperm parameters were normal. Right epididymis and liver weights, relative to body weight, were increased (12 and 23%, respectively) over the control group for high-dose males. A mating trial to determine the fertility and reproductive competence of the F1 generation showed no effect of CARI on indices of mating, pregnancy, or fertility, the proportion of F2 pups born alive, the sex ratio of live F2 pups, live F2 pup weight, or gestation length.(ABSTRACT TRUNCATED AT 250 WORDS)

Carisoprodol elimination in humans.

The elimination of the muscle relaxant drug, carisoprodol, was examined in 10 healthy volunteers after an oral dose of 700 mg. In nine subjects, carisoprodol was rapidly eliminated, with a mean half-life of 99 +/- 46 min, and extensively converted to meprobamate. Within 2.5 h after carisoprodol intake, meprobamate serum concentrations exceeded those of carisoprodol. Serum levels of meprobamate recorded (15-25 mumol/L) indicate that meprobamate might contribute to the effect(s) of carisoprodol. One subject eliminated carisoprodol with an overall half-life of 376 min, and only small amounts of meprobamate were recorded. This subject was found to be a poor metabolizer of mephenytoin. In spiked human sera, protein binding of carisoprodol was in the range of 41-67%, whereas meprobamate was bound to a lesser extent, 14-24%.

Carisoprodol abuse: a report from India.

Carisoprodol, a centrally acting muscle relaxant, has recently been noticed to be abused. A series of 16 cases with carisoprodol abuse or dependence is described. Carisoprodol was started by the majority of patients as a substitute for opiates, although its independent distinct effects, similar to the features of hypomania, were recognized and described by most users. The drug is currently available freely over the counter and is a much cheaper substitute for the legally prohibited "harder" drugs. Unless awareness spreads and cautionary measures are taken, carisoprodol abuse might become a great menace in the near future.

Carisoprodol (Soma): a new and cautious perspective on an old agent.

Transformation of BALB/c-3T3 cells: IV. Rank-ordered potency of 24 chemical responses detected in a sensitive new assay procedure.

This report introduces an improved method of detecting chemical-induced morphological transformation of A-31-1-13 BALB/c-3T3 cells. The new procedure uses an increased target cell population to assess chemical-induced damage by increasing the initial seeding density and by delaying the initiation time of chemical treatment. Furthermore, a newly developed co-culture clonal survival assay was used to select chemical doses for the transformation assay. This assay measured the relative cloning efficiency (RCE) of chemical treatments in high-density cell cultures. In addition, transformation assay sensitivity was enhanced through the use of improved methods to solubilize many chemicals. From a group of 24 chemicals tested in at least two trials, clear evidence of chemical-induced transformation was detected for 12 chemicals (aphidicolin, barium chloride-2H2O, 5-bromo-2-deoxyuridine, C.I. direct blue 15, trans-cinnamaldehyde, cytosine arabinoside, diphenylnitrosamine, manganese sulfate-H2O, 2-mercaptobenzimidazole, mezerein, riddelliine, and 2,6-xylidine); 2 chemicals had equivocal activity [C.I. direct blue 218 and mono(2-ethylhexyl)phthalate], 9 chemicals were inactive [carisoprodol, chloramphenicol sodium succinate, 4-chloro-2-nitroaniline, C.I. acid red 114, isobutyraldehyde, mono(2-ethylhexyl)adipate, sodium fluoride, and 12-O-tetradecanoylphorbol-13-acetate), and 1 chemical had an indeterminate response (2,6-dinitrotoluene). All positive responses were detected in the absence of an exogenous activation system and exhibited significant activity at two or more consecutive doses. This report also presents a mathematical method that uses t-statistics for rank-ordering the potency of chemical-induced transformation responses. This model detects sensitivity differences in experiments used to evaluate chemical-induced transformation. Furthermore, it provides a method to estimate a chemicals transformation response in terms of the historical behavior of the assay, as well as its future activity. The most active of the 24 chemicals was mezerein, and the least active chemical was diphenylnitrosamine.

Carisoprodol as a drug of abuse.

Carisoprodol (available as Soma and in other commercial forms) is a commonly prescribed muscle relaxant. A small group of patients was recently discovered colluding to obtain the drug under false pretenses for the purposes of substance abuse. Animal and human studies have previously shown limited potential for tolerance or abuse, while the evidence for therapeutic efficacy is inadequate. There are two previous case reports of human carisoprodol abuse or dependence, one in which a patient showed signs of a true withdrawal syndrome. A third case involved a fatality linked to carisoprodol abuse. Data from the National Institute on Drug Abuse reveal that overdose and abuse of carisoprodol may be more common than previously suspected. Carisoprodol use should be limited to short-term treatment of acute musculoskeletal conditions involving significant muscle spasm. Suspicions of abuse should be raised by patients requesting the drug by name, "losing" prescriptions, using carisoprodol chronically, or denying the efficacy of less mind-altering alternatives.

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