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Muscle Relaxant Activity (muscle + relaxant_activity)
Selected AbstractsNew metabolic and pharmacokinetic characteristics of thiocolchicoside and its active metabolite in healthy humansFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2004M. Trellu Abstract Thiocolchicoside (TCC) has been prescribed for several years as a muscle relaxant drug, but its pharmacokinetic (PK) profile and metabolism still remain largely unknown. Therefore, we re-investigated its metabolism and PK, and we assessed the muscle relaxant properties of its metabolites. After oral administration of 8 mg (a therapeutic dose) of 14C-labelled TCC to healthy volunteers, we found no detectable TCC in plasma, urine or faeces. On the other hand, the aglycone derivative obtained after de-glycosylation of TCC (M2) was observed and, in addition, we identified, as the major circulating metabolic entity, 3-O-glucuronidated aglycone (M1) obtained after glucuro-conjugation of M2. One hour after oral administration, M1 plus M2 accounted for more than 75% of the circulating total radioactivity. The pharmacological activity of these metabolites was assessed using a rat model, the muscle relaxant activity of M1 was similar to that of TCC whereas M2 was devoid of any activity. Subsequently, to investigate the PK profile of TCC in human PK studies, we developed and validated a specific bioanalytical method that combines liquid chromatography and ultraviolet detection to assay both active entities. After oral administration, TCC was not quantifiable with an lower limit of quantification set at 1 ng/mL, whereas its active metabolite M1 was detected. M1 appeared rapidly in plasma (tmax = 1 h) and was eliminated with an apparent terminal half-life of 7.3 h. In contrast, after intramuscular administration both active entities (TCC and M1) were present; TCC was rapidly absorbed (tmax = 0.4 h) and eliminated with an apparent terminal half-life of 1.5 h. M1 concentration peaked at 5 h and this metabolite was eliminated with an apparent terminal half-life of 8.6 h. As TCC and M1 present an equipotent pharmacological activity, the relative oral pharmacological bioavailability of TCC vs. intramuscular administration was calculated and represented 25%. Therefore, to correctly investigate the PK and bioequivalence of TCC, the biological samples obtained must be assayed with a bioanalytical method able to specifically analyse TCC and its active metabolite M1. [source] 1,8-Cineole induces relaxation in rat and guinea-pig airway smooth muscleJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2009Nilberto Robson Falcão Nascimento Abstract Objectives 1,8-Cineole is a monoterpene with anti-inflammatory, vascular and intestinal smooth muscle relaxant activity. We have evaluated the potential bronchodilatatory activity of this compound. Methods 1,8-Cineole was tested against carbachol, histamine, K+ 80 mM and ovalbumin-induced bronchial contractions in Wistar rat or guinea-pig tissues. Some of the guinea-pigs had been previously sensitized with an intramuscular injection of 5% (w/v) ovalbumin/saline solution. Control animals received 0.3 ml saline. In separate experimental groups the response to 1,8-cineole (1,30 mg/kg), phenoterol (0.05,5 mg/kg) or vehicle (0.3% Tween in saline) was studied. Key findings 1,8-Cineole decreased, in vivo, rat bronchial resistance with similar efficacy as phenoterol (66.7 ± 3.2% vs 72.1 ± 5.3%). On the other hand, the maximal relaxant response to 1,8-cineole in carbachol-precontracted rat tracheas was 85.5 ± 5.7% (IC50 = 408.9 (328,5196) ,g/ml) compared with 80.2 ± 4.8% (IC50 = 5.1 (4.3,6.1) ,g/ml) with phenoterol. The addition of 1,8-cineole to guinea-pig tracheal rings tonically contracted with K+ 80 mM induced a concentration-related relaxation. The maximal relaxation elicited by 1,8-cineole was 113.6 ± 11.7% (IC50 127.0 (115.9,139.2) ,g/ml) compared with 129.7 ± 14.6% (IC50 0.13 (0.12,0.14) ,g/ml) achieved after phenoterol administration. In addition, the incubation of tracheal rings with 1,8-cineole (100, 300 or 1000 ,g/ml), 15 min before inducing phasic contractions with K+ 80 mM, decreased the maximal amplitude of the contraction by 31.6 ± 4.6, 75.7 ± 2.7 and 92.2 ± 1.5%, respectively. In another set of experiments, neither the maximal response nor the IC50 for the 1,8-cineole-induced relaxation were different between normal and ovalbumin-sensitized tissues. Moreover, the relaxation of bronchial rings contracted after exposure to 1 ,g/ml ovalbumin occurred at a faster rate in rings pre-incubated with 1,8-cineole when compared with rings pre-incubated with vehicle only (Tween 0.3%). Therefore, in the first minute after the antigen challenge, the tracheal tissue relaxed after the peak contraction by 6.5, 21.4 (P < 0.05 vs control) and 66.9% (P < 0.05 vs control) in the presence of 100, 300 or 1000 ,g/ml 1,8-cineole, respectively. Conclusions 1,8-Cineole relaxed rat and guinea-pig (nonsensitized and ovalbumin-sensitized) airway smooth muscle by a nonspecific mechanism. [source] Antispasmodic activity of licochalcone A, a species-specific ingredient of Glycyrrhiza inflata rootsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2007Hidemasa Nagai Licochalcone A, a species-specific and characteristic retrochalcone ingredient of Glycyrrhiza inflata root, has been shown to possess multiple bioactive properties. However, its muscle relaxant activity has not been reported previously. Licochalcone A showed a concentration-dependent relaxant effect on the contraction induced by carbachol (50% effective concentration (EC50) = 5.64 ± 1.61 ,m). KCl (EC50 5.12 ± 1.68 ,m), BaCl2 (EC50 1.97 ± 0.48 ,m) and A23187 (EC50 2.63 ± 2.05 ,m). Pretreatment with licochalcone A enhanced the relaxant effect of forskolin, an adenylyl cyclase activator, on the contraction in a similar manner to 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase (PDE) inhibitor. Furthermore, the IC50 (22.1 ± 10.9 ,m) of licochalcone A against cAMP PDE was similar to that of IBMX (26.2 ± 7.4 ,m). These results indicated that licochalcone A may have been responsible for the relaxant activity of G. inflata root and acted through the inhibition of cAMP PDE. [source] Studies on psychopharmacological effects of Cleome viscosa Linn. extract in rats and micePHYTOTHERAPY RESEARCH, Issue 2 2004B. Parimala Devi Abstract Methanol extract of the entire plant Cleome viscosa Linn. (CVME) was evaluated for different psychopharmacological actions such as general behaviour, exploratory behaviour, muscle relaxant activity and phenobarbitone induced sleeping time and effects on normal body temperature in rats and mice. The extract was found to cause reduction in spontaneous activity, decrease in exploratory behavioural pattern by the head dip and Y-maze test, reduction in the muscle relaxant by rotarod, 30° inclined screen and traction tests and caused signi,cant lowering of body temperature. In addition, CVME signi,cantly potentiated the phenobarbitone-induced sleeping time. Preliminary tests indicate that the methanol extract of Cleome viscosa Linn. in doses of 200,400 mg/kg has signi,cant psychopharmacological activity. Copyright © 2004 John Wiley & Sons, Ltd. [source] | ||||||||||