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PubMedDate not supplied

The L6 muscle cell line as a tool to evaluate parenteral products for irritation.

A rat skeletal muscle cell line (L6) was evaluated for its utility in assessing cellular damage caused by parenteral administration of eight commercially available pharmaceuticals. The physical forms of the eight pharmaceuticals were diverse, including aqueous and non-aqueous suspensions and solutions. The L6 cells were exposed to therapeutic as well as diluted concentrations of methocarbamol, lorazepam, dimercaprol, phytonadione, menadiol sodium phosphate, penicillin G procaine, penicillin G benzathine, and iron dextran complex. Irritation assessment was based on the depletion of creatine phosphokinase (CK) from treated cultures versus untreated controls. The results obtained correlate well with reports of irritation and side effects noted in clinical use, and demonstrate the versatility of the model for testing suspensions and non-aqueous parenteral solutions. The L6 model is a useful tool to assist in determining the relative local irritancy of parenteral products.

Animals↗

PubMedDate not supplied

[Review of latrodectism and Malmignatta sting (Latrodectus tredecimguttatus) in Italy].

The latrodectism is a rare poisoning rather unknown in Italy and some times fatal. The Authors in this latrodectism review intend to provide information about the Malmignatta spider Latrodectus tredecimguttatus: biology, Italian distribution and peculiarity of its venom. Here are reported the clinical picture of the toxic syndrome, with first principles of differential diagnosis. Afterwards, they face the treatment, illustrating the cases where they can use the antivenom, calcium gluconate or methocarbamol, with modalities, doses and administration stages.

Animals↗

PubMed1990

Skeletal muscle relaxant ingestion.

We retrospectively analyzed 56 consecutive cases involving acute skeletal muscle relaxant exposure that were reported to the Poison Control Center over a 1-year period. The age range was 9 mo to 56 years (mean 18.9 +/- 13.1) with the site of exposure being the primary residence in 54 cases (96.4%). The reasons for inquiry to the Poison Center were reported to be intentional suicide in 26 cases (46.4%), accidental in 21 cases (37.5%), with intentional misuses in 5 cases (8.9%). No deaths were reported. Eighteen cases (32.1%) were reported with co-ingestants (average number of substances taken was 2.7 +/- 0.8). Of these cases 3 patients (16.7%) had major effects with life-threatening symptoms with 6 (33.3%) patients having no symptoms. Of the remaining 38 cases, 17 (44.7%) wer cyclobenzaprine, 6 (15.8%) were methocarbamol, 5 (13.2%) were carisoprodol, 5 (13.2%) were chlorzoxazone, 3 (7.89%) were Baclofen and the remainder were either life-threatening symptoms (2.6%), while 29 (74.3%) had no or minor effects with symptoms that subsided. We conclude that morbidity and mortality are low in pure skeletal muscle relaxant ingestion, however it may be increased in multiple ingestions.

Adolescent↗

PubMed1980

Centrally acting oral skeletal muscle relaxants.

A critical examination of the literature on centrally acting, orally administered skeletal muscle relaxants (SMRs) is presented. The available comparative clinical studies are reviewed, and the pharmacology, metabolism and adverse effects of the oral SMRs are discussed briefly. The drugs covered are carisoprodol, chlorphenesin carbamate, chlorzoxazone, cyclobenzaprine hydrochloride, diazepam, metaxalone, methocarbamol, and orphenadrine citrate. The mechanism of action of these agents is not well defined, and their effects are measured mainly by subjective responses. Thus, acceptable evidence of efficacy is difficult to obtain, especially if clinical studies continue to be designed inadequately. There are inadequate data to support the superiority of any one drug. Further, unique clinical efficacy of any oral SMR in comparison to nonspecific sedation has not been established. Based on subjective responses, all agents, except diazepam, have been shown to be superior to placebo in acute disorders; cyclobenzaprine has not been evaluated in acute conditions. SMRs are less effective in chronic disorders. Combination muscle relaxant-analgesic products appear to be superior to their individual components, but the relative efficacy of these combination products in comparison to combined use of individual sedative and analgesic agents is unknown.

Analgesics↗

PubMed1982

Forelimb tic in a horse.

An 18-month-old male Quarter Horse was referred for evaluation of a tic that had started after injury to the right forelimb 4 weeks earlier. The right forelimb appeared paretic and had constant regular twitches of variable intensity that were usually sufficiently forceful to move the trunk, neck, and head. The horse frequently threw the limb forward. The twitch persisted during sleep but disappeared during general anesthesia and following sedation with xylazine. It was unaffected by acetylpromazine, diphenylhydantoin, diazepam, carbamazepine, trimethadione, procainamide, quinidine, propranolol, dantrolene, methocarbamol, dimethyl sulfoxide mixed with xylocaine, or by low volar nerve anesthesia. It remained unchanged during 21 days of hospitalization but had stopped 10 weeks after discharge. Electromyographic tracings of the limb and neck and radiographs of the cervical and proximal thoracic spine, scapulohumeral joints, and adjacent ribs were normal. A localized spinal cord lesion or peripheral neuropathy and neuralgia secondary to trauma were suspected.

Animals↗

PubMed1993

Pharmacological specificity of the discriminative stimulus properties of 2-amino-4,5-(1,2-cyclohexyl)-7-phosphono-heptanoic acid (NPC 12626), a competitive N-methyl-D-aspartate receptor antagonist.

A drug discrimination based upon the competitive N-methyl-D-aspartate (NMDA) antagonist 2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid (NPC 12626) was assessed for pharmacological specificity. Adult male Sprague-Dawley rats were trained to discriminate 20 mg/kg i.p. of NPC 12626 from saline under a standard two-lever fixed ratio 32 schedule of food reinforcement. Stimulus generalization tests were conducted to examine the similarities and differences between NPC 12626, its active (2R,4R,5S) enantiomer NPC 17742, other competitive and noncompetitive NMDA antagonists and a number of drugs representative of other classes. During test sessions, the competitive NMDA antagonists NPC 12626, CGS 19755, [1-(cis-2-carboxypiperidine-4-yl)- methyl-1-phosphonic acid], NPC 17742, CSP 37849 [DL-(E)-2-amino-4-methyl-5-phosphono-3-pen-tenoic acid] and CPPene [D-3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid] all completely substituted for the training dose of NPC 12626 with ED50 values of 18.1, 2.3, 2.1, 0.8 and 0.8 mg/kg, respectively. In contrast, drugs that failed to substitute for NPC 12626 included (+)-amphetamine, baclofen, chlorpromazine, dextromethorphan, diazepam, dizocilpine (MK-801), imipramine, (-)-ketocyclazocine, L-N6-phenylisopropyladenosine, methocarbamol, morphine, muscimol, phenytoin, physostigmine and valproate. These results provide evidence that the NPC 12626 discriminative stimulus is unique and specific, shared fully only by its active enantiomer NPC 17742 and other competitive NMDA antagonists. This specificity provides further support for the hypothesis of NMDA receptor mediation of NPC 12626 discrimination, and suggests that this is a useful model to evaluate behavioral effects of competitive NMDA antagonists.

Amino Acids↗

PubMed1963