RESUMEN
Silicone-made tissue cages were implanted in sheep. Blood serum (SBS) and tissue cage fluid (TCF) samples were collected after amoxicillin intravenous and intramuscular administrations, at the dose of 15 mg/kg. Amoxicillin pharmacodynamics were studied in an artificial culture medium, SBS and TCF with use of a Mannheimia haemolytica and a Pasteurella multocida strain. A concentration-independent antimicrobial activity of amoxicillin was confirmed for levels higher than 0.79-1.75×MIC. This result favored the use of the percentage of the 24 h dosing interval during which drug levels remain above MIC as the appropriate pharmacokinetic/pharmacodynamic index. The subsequent correlation revealed that intravenous administration could be considered effective against "deep" infections caused by bacteria with MICs<1 µg/mL or "shallow" infections caused by bacteria with MICs<0.1 µg/mL. Intramuscular administration could be safely considered effective against both "deep" and "shallow" infections when the MICs of the targeted pathogens are lower than 1 µg/mL.
Asunto(s)
Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Mannheimia haemolytica/efectos de los fármacos , Infecciones por Pasteurella/veterinaria , Pasteurella multocida/efectos de los fármacos , Infecciones por Pasteurellaceae/veterinaria , Enfermedades de las Ovejas/tratamiento farmacológico , Amoxicilina/administración & dosificación , Amoxicilina/farmacocinética , Animales , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Relación Dosis-Respuesta a Droga , Inyecciones Intramusculares/veterinaria , Inyecciones Intravenosas/veterinaria , Pruebas de Sensibilidad Microbiana/veterinaria , Infecciones por Pasteurella/tratamiento farmacológico , Infecciones por Pasteurellaceae/tratamiento farmacológico , Ovinos , Enfermedades de las Ovejas/microbiologíaRESUMEN
The pharmacokinetics of amoxicillin (AMX) were investigated in sheep following intravenous (i.v.) and intramuscular (i.m) injection, comparing two different drug formulations, a conventional and a long-acting AMX-trihydrate suspension. For the i.m. application two different injections sites, the neck area and the hind limb were used to identify possible differences in the kinetic parameters related to the site of injection. A three-compartment open model could best describe AMX disposition after i.v. administration. Data analysis after i.m. administration of the conventional suspension at both injection sites revealed the occurrence of a flip-flop phenomenon, clearly indicating that absorption of AMX is the rate-limiting step of its overall disposition. A moderate effect of the injection site was observed with a tendency for the neck area to be advantageous, mainly in terms of rate rather than extent of absorption. Injection of the long-acting formulation led to a focal depot formation, thus yielding lower but remarkably prolonged serum AMX levels reflected in the respective terminal half-lives. The concentration-time profile of AMX after administration of the long-acting formulation was less affected by the injection site, but the low serum levels justify its use only in cases in which a high susceptibility of the involved bacterial population is confirmed.
Asunto(s)
Amoxicilina/administración & dosificación , Antibacterianos/administración & dosificación , Amoxicilina/sangre , Amoxicilina/farmacocinética , Animales , Antibacterianos/sangre , Antibacterianos/farmacocinética , Preparaciones de Acción Retardada , Miembro Posterior , Inyecciones Intramusculares/veterinaria , Inyecciones Intravenosas/veterinaria , Masculino , Cuello , Unión Proteica , Ovinos/metabolismo , SuspensionesRESUMEN
This study demonstrates that the inotropic agent milrinone and the bronchodilator drug theophylline exert a relaxing effect on the rabbit lower oesophageal sphincter in vitro. The relaxing effect of milrinone and theophylline, which is concentration-dependent, involves a second messenger 3',5'-cyclic adenosine monophosphate pathway and most probably it is accomplished through inhibition of phosphodiesterase (PDE) type III, as according to the obtained results it is not significantly modified either by nicotinic acid, an inhibitor of adenylate cyclase, or by the inhibitor of nitric oxide-synthetase N(omega)-nitro-L-arginine methylester and the purinergic antagonist suramin; moreover, it persists under non-adrenergic non-cholinergic conditions and it is both hexamethonium- and tetrodotoxin-insensitive. Both milrinone and theophylline display equal efficacy, comparable to that of the calcium blocker verapamil and the non-selective PDE inhibitor papaverine, but milrinone appears 50 times more potent than theophylline and three times less potent than verapamil, as, according to the pIC(50) values the potency rank of order is found to be verapamil (5.56) > milrinone (5.12) > theophylline (3.42). The here obtained pharmacodynamic profiles of the drugs suggest that both milrinone and theophylline may be considered as potent relaxing agents of the lower oesophageal sphincter.
Asunto(s)
Broncodilatadores/farmacología , Esfínter Esofágico Inferior/efectos de los fármacos , Milrinona/farmacología , Relajación Muscular/efectos de los fármacos , Teofilina/farmacología , Vasodilatadores/farmacología , Animales , Esfínter Esofágico Inferior/fisiología , Femenino , Masculino , Papaverina/farmacología , Conejos , Verapamilo/farmacologíaRESUMEN
The present study examines comparatively the effects of theophylline and its metabolites, 1-methylxanthine (1-MX), 3-methylxanthine (3-MX), 1,3-dimethyluric acid (1,3-DMU) and 1-methyluric acid (1-MU) along the rabbit intestine, and explores the underlying mechanism(s). In the small intestine, theophylline produces atropine- and hexamethonium-sensitive increases in both the amplitude of phasic contractions and the basal tone. All metabolites mimic the theophylline's stimulating effect. In particular, concerning the phasic contractions, all metabolites are more potent than theophylline in the duodenum and jejunum, while in the ileum, only 1-MU is more potent. Regarding the basal tone, the metabolites show, in most cases, higher efficacy in all small intestinal regions, the maximum effects of 3-MX and 1-MU on the duodenum and ileum being double or triple the one of theophylline. In the ascending colon, while lower concentrations of theophylline produce an atropine- and hexamethonium-sensitive increase in the basal tone, higher ones produce a postsynaptic, nonadrenergic noncholinergic (NANC) relaxing effect. 1-MU mimics, in a weaker manner, theophylline's effect, while the other metabolites produce only relaxation, the potency rank of order being 3-MX>1-MX=1,3-DMU>theophylline. It is suggested that the theophylline and its metabolites stimulatory effect involves a cholinergic pathway, while the relaxing one is due to 3('),5(')-cyclic adenosine monophosphate (cAMP) elevation mediated by the theophylline and its metabolites inhibitory action on phosphodiesterases (PDEs).
Asunto(s)
Broncodilatadores/farmacología , Colon/efectos de los fármacos , Intestino Delgado/efectos de los fármacos , Teofilina/farmacología , Animales , Broncodilatadores/administración & dosificación , Colon/fisiología , Relación Dosis-Respuesta a Droga , Femenino , Intestino Delgado/fisiología , Masculino , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Conejos , Teofilina/administración & dosificaciónRESUMEN
The combination of sulphadiazine and trimethoprim is extensively used in farm animal species; however, there are no data concerning its pharmacokinetics after intramuscular administration in sheep. Twelve rams of the Chios breed were used to study the disposition of sulphadiazine, its metabolite N4-acetylsulphadiazine and trimethoprim after intravenous (i.v.) and intramuscular (i.m.) administration of a sulphadiazine/trimethoprim (5:1) combination in sheep. Sulphadiazine bioavailability (+/-SD) was 69.00%+/-10.51%. The half-life of the terminal phase (4.10+/-0.58 h after i. v., and 4.03+/-0.31 h after i.m. administration) was significantly higher than the respective value for trimethoprim (0.59+/-0.19 h) after i.v. administration. The maintenance of a constant plasma concentration ratio after i.v. administration was therefore impossible. The acetylation capacity in sheep, determined by the AUC ratio between N4-acetylsulphadiazine and the parent compound, sulphadiazine, was very low (less than 4%). The most remarkable finding of this study was that trimethoprim was not detected in sheep plasma after i.m. injection. In conclusion, according to the findings of the present study, following i.v. administration of the sulphadiazine/trimethoprim combination, trimethoprim can be considered as the limiting factor for any possible synergistic effect, and the i.m. route cannot be recommended in sheep.
Asunto(s)
Antiinfecciosos Urinarios/farmacocinética , Ovinos/metabolismo , Sulfadiazina/farmacocinética , Trimetoprim/farmacocinética , Animales , Antiinfecciosos Urinarios/administración & dosificación , Área Bajo la Curva , Disponibilidad Biológica , Estudios Cruzados , Combinación de Medicamentos , Sinergismo Farmacológico , Semivida , Inyecciones Intramusculares/veterinaria , Inyecciones Intravenosas/veterinaria , Masculino , Tasa de Depuración Metabólica , Sulfadiazina/administración & dosificación , Trimetoprim/administración & dosificaciónRESUMEN
A new HPLC method for the quantitative determination of clindamycin in dog blood serum at levels down to 80 ng/ml has been developed. Samples were deproteinised with acetonitrile and clindamycin was extracted with dichloromethane. Chromatographic analysis was carried out on a C(18) reversed-phase analytical column in the presence of tetra-n-butylammonium hydrogen sulfate (TBA), as an ion-pairing agent. UV detector wavelength was set at 195 nm. The assay was validated for a concentration range from 80 to 6000 ng/ml serum. Good linearity was observed in the entire concentration range. The limit of quantification (LOQ) was 80 ng/ml and the limit of detection (LOD) was 60 ng/ml. Regression of accuracy data yielded an overall mean recovery value (+/-S.E.M.) of 93.98+/-0.42%, while precision data revealed coefficient of variation (CV (%)) values lower than 4.41%. The method was successfully applied to determine drug concentrations in serum samples from dogs that had been orally administered clindamycin hydrochloride.
Asunto(s)
Cromatografía Líquida de Alta Presión/veterinaria , Clindamicina/sangre , Espectrofotometría Ultravioleta/veterinaria , Tecnología Farmacéutica/métodos , Animales , Cromatografía Líquida de Alta Presión/métodos , Clindamicina/análisis , Enfermedades de los Perros/sangre , Enfermedades de los Perros/tratamiento farmacológico , Perros , Estabilidad de Medicamentos , Espectrofotometría Ultravioleta/métodosRESUMEN
The present investigation aims to examine whether the prokinetic agent cisapride is able to reverse disopyramide's anticholinergic effect on the isolated guinea-pig urinary bladder. Acetylcholine, at concentrations ranging from 10(-7) to 10(-3) M, produced a stimulatory effect on the urinary bladder (pEC(50) value=5.1). Disopyramide competitively antagonized the contractile effect of acetylcholine with an ID(50)=4.4 x 10(-6) M. Although cisapride by itself had either no intrinsic contractile action or a modest effect on the urinary bladder, at concentrations ranging from 3 x 10(-7) to 10(-6) M, it significantly reversed the above inhibitory effect of disopyramide, and produced a parallel leftward shift of the concentration-response curve for acetylcholine in the presence of disopyramide. The pEC(50) values for acetylcholine in the presence of 3 x 10(-6) M and 10(-5) M disopyramide were 4.7 and 4.2, respectively, while in the presence of 10(-5) M disopyramide, after pretreatment with 5 x 10(-7) M cisapride, the pEC(50) value for acetylcholine was 4.6. It is concluded that cisapride is effective in reversing the anticholinergic activity of disopyramide on the isolated guinea-pig urinary bladder, probably by facilitating cholinergic neurotransmission.
Asunto(s)
Antagonistas Colinérgicos/farmacología , Cisaprida/farmacología , Disopiramida/farmacología , Fármacos Gastrointestinales/farmacocinética , Vejiga Urinaria/efectos de los fármacos , Acetilcolina/farmacología , Animales , Cisaprida/administración & dosificación , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Femenino , Fármacos Gastrointestinales/administración & dosificación , Cobayas , Masculino , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Sistema Nervioso Parasimpático/efectos de los fármacos , Parasimpatolíticos/farmacologíaRESUMEN
This paper examines the effect of biphenylacetic acid on the antagonistic action of norfloxacin and enoxacin on the GABA(A)-mediated responses of the isolated guinea-pig ileum. GABA produced transient contractions followed by relaxation. The contractile effect of exogenously applied GABA was concentration-dependent with EC(50)= 9.8 x 10(-6) M. This contractile effect was not significantly modified by biphenylacetic acid, and the EC(50) value for GABA in the presence of 10(-5) M biphenylacetic acid was 1.15 x 10(-5) M. The GABA contractile effect was inhibited, dose-dependently, by either norfloxacin or enoxacin, but only at concentrations higher than 10(-5) M. The response of the ileum to GABA (at EC(50)) was reduced to 35 and 36% by pretreatment with 10(-5) M norfloxacin or enoxacin, respectively. However, in the presence of 10(-5) M biphenylacetic acid, the response of the ileum to GABA was reduced to 2.2% by pretreatment with 10(-5) M enoxacin, while it was completely abolished by pretreatment with 10(-5) M norfloxacin and the IC(50) values were 5.5 x 10(-7) and 1.5 x 10(-6) M for norfloxacin and enoxacin, respectively. These data show that biphenylacetic acid whilst having no effect at the GABA(A)-mediated contractile response of the guinea-pig ileum, enhances the antagonistic effect of both enoxacin and norfloxacin. This suggests that combined administration of fluoroquinolones and biphenylacetic acid synergistically inhibits GABA(A)-receptors at the intestinal level.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Fluoroquinolonas/farmacología , Íleon/efectos de los fármacos , Fenilacetatos/farmacología , Receptores de GABA-A/fisiología , Animales , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Femenino , Cobayas , Íleon/fisiología , Técnicas In Vitro , Masculino , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiologíaRESUMEN
The present study examines the pharmacodynamic interaction between the H(2)-receptor antagonist ranitidine and the prokinetic agent cisapride on the isolated rabbit intestine. Ranitidine produced a concentration-dependent contractile effect on the duodenal, ileal and ascending colon preparations, with EC(50)values of 1.35 x 10(-4)M for the duodenum, 1.2 x 10(-4)M for the ileum and 1.15 x 10(-4)M for the ascending colon. The effect of cisapride on the ranitidine contractile effect was dependent on the cisapride concentration used. Thus, cisapride, at concentrations from 10(-10)up to 5 x 10(-7)for the duodenum and the ascending colon and up to 10(-6)M for the ileum, potentiated the contractile responses of the preparations to ranitidine. However, at higher concentrations cisapride produced a non-competitive inhibition of the intestinal contractile responses to ranitidine with IC(50)values of 4.2 x 10(-5)M for the duodenum, 1.65 x 10(-5)M for the ileum and 3.2 x 10(-6)M for the ascending colon. These data show that cisapride may modify the contractile responses of the isolated rabbit intestine to ranitidine, having a potentiating effect up to a certain concentration and an antagonistic one at higher concentrations. In conclusion, co-administration of the above drugs may lead to enhanced or reduced intestinal motility.
Asunto(s)
Cisaprida/farmacología , Fármacos Gastrointestinales/farmacología , Intestinos/efectos de los fármacos , Ranitidina/farmacología , Animales , Colon/efectos de los fármacos , Colon/fisiología , Relación Dosis-Respuesta a Droga , Antagonismo de Drogas , Sinergismo Farmacológico , Femenino , Motilidad Gastrointestinal/efectos de los fármacos , Íleon/efectos de los fármacos , Íleon/fisiología , Técnicas In Vitro , Intestinos/fisiología , Masculino , ConejosRESUMEN
A trial was carried out with HYORESP a Mycoplasma hyopneumoniae (M. hyo) vaccine in order to confirm the benefit of vaccination under field conditions in a commercial industrial farrow-to-finish unit, contaminated with M. hyo. Infection with M. hyo was confirmed through positive blood and colostrum samples [enzyme-linked immunosorbent assay (ELISA) test] combined with positive gross lesions of the lung at slaughter. Two different vaccination schedules were tested. Pigs were randomly allocated to three groups: control non-vaccinated group (n = 130, given a placebo injection at 3, 25 and 70 days of age); early vaccinated group (n = 128, given vaccination at 3 and 25 days of age and a placebo at 70 days of age); late vaccinated group (n = 132, given a placebo at 3 and 25 days of age and vaccination at 70 days of age). Both growth rate and feed conversion ratio were signifcantly (P < 0.05) improved in the vaccinated groups compared with the control group. The lung lesion score was also significantly (P < 0.05) improved in both vaccinated groups. In this trial, it was clearly demonstrated that vaccination is highly effective in improving performance in pig units infected with M. hyo. The improvement in the feed conversion ratio in the vaccinated groups was especially impressive: -0.411 (13% improvement) in the group vaccinated twice at 3 and 25 days of age; -0.162 (5% improvement) in the group vaccinated once at 70 days of age. Performances were better when two shots were given early in life compared with one shot later--probably due to an infection taking place rather early in life for most of the pigs. Moreover, a significant reduction in the cost of supportive (injectable) medication was noticed in vaccinated pigs. In conclusion, HYORESP proved to be a very efficacious tool to control M. hyo in infected herds with its remarkable flexibility that allows the vaccination schedule to be adapted to the specific field conditions.
Asunto(s)
Vacunas Bacterianas/administración & dosificación , Infecciones por Mycoplasma/veterinaria , Mycoplasma/inmunología , Enfermedades de los Porcinos/prevención & control , Factores de Edad , Animales , Vacunas Bacterianas/inmunología , Femenino , Crecimiento , Esquemas de Inmunización , Masculino , Infecciones por Mycoplasma/inmunología , Infecciones por Mycoplasma/prevención & control , Porcinos , Enfermedades de los Porcinos/inmunología , Vacunación/veterinariaRESUMEN
This study examines the effect of the anaesthetic agent propofol on the guinea pig ileum and whether this effect derives from an interaction of the drug with GABA receptors. Propofol produced a biphasic effect consisting of a dose-dependent contractile effect (EC(50)=2.2x10(-5)m) followed by an 'after relaxation'. This propofol effect was similar to the one produced by GABA and was bicuculline-sensitive (ID(50)=3.2x10(-7)m). Propofol, at concentrations of 10(-7)and 10(-6)m, potentiated the ileum contractile responses to GABA, but only at the lower dose range of applied GABA, while at a concentration of 10(-5)m, it inhibited the contractile effect over the entire dose range of applied GABA. In addition, while the contractile response of the ileum to exogenously applied acetylcholine was not influenced by propofol at concentrations of up to 7x10(-6)m, it was antagonised by higher concentrations of propofol. In conclusion, the above data permit us to suggest that propofol's contractile effect on the guinea pig ileum is mediated by an interaction of the drug with GABA(A)-receptors.
Asunto(s)
Anestésicos Intravenosos/farmacología , Íleon/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Propofol/farmacología , Receptores de GABA-A/efectos de los fármacos , Acetilcolina/farmacología , Animales , Bicuculina/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Antagonistas del GABA/farmacología , Cobayas , Íleon/fisiología , Masculino , Contracción Muscular/fisiología , Receptores de GABA-A/fisiología , Vasodilatadores/farmacología , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
This study examines the influence of the prokinetic agent cisapride on the disopyramide's effect on the isolated duodenum and ileum, as well as on the ascending colon of the guinea pig. Acetylcholine produced the well known stimulatory effect on the intestinal parts with EC50 values 9.6 x 10(-8), 7 x 10(-9) and 1.1 x 10(-6) M for the duodenum, ileum and ascending colon, respectively. Disopyramide inhibited, in a concentration-dependent manner, the contractile responses of the intestinal parts to acetylcholine. Cisapride, at concentrations ranging from 5 x 10(-9) M to 10(-6) M, significantly reversed the above inhibitory effect of disopyramide on the guinea pig duodenum and ileum and produced a parallel leftward shift of the concentration-response curve for acetylcholine in the presence of disopyramide. However, cisapride was not found able to reverse the inhibitory effect of disopyramide on the ascending colon. In conclusion, cisapride may counteract the inhibitory effect of disopyramide on the guinea pig duodenum and ileum, probably by facilitating the cholinergic neurotransmission, while it is not able to reverse the disopyramide's inhibitory effect on the guinea pig ascending colon.
Asunto(s)
Antiarrítmicos/farmacología , Cisaprida/farmacología , Disopiramida/farmacología , Fármacos Gastrointestinales/farmacología , Motilidad Gastrointestinal/efectos de los fármacos , Intestino Grueso/efectos de los fármacos , Intestino Delgado/efectos de los fármacos , Acetilcolina/farmacología , Animales , Interacciones Farmacológicas , Femenino , Cobayas , Técnicas In Vitro , Intestino Grueso/fisiología , Intestino Delgado/fisiología , MasculinoRESUMEN
1. In this study, the effect of cisapride on the isolated guinea pig gall bladder (GB) and common bile duct (CBD) motility was investigated. 2. Cisapride, up to a certain concentration, produced an increase in tone of the GB (EC50 1.35 x 10(-8) M) and the CBD (EC50 2.75 x 10(-9) M), whereas, at concentrations higher than 3 x 10(-5) M for the GB and 5 x 10(-6) M for the CBD, it produced a transient increase in tone followed by a sustained decrease in tone or in the contraction amplitude or in both. 3. The cisapride-induced increase in tone was antagonized by atropine on both the GB and the CBD. 4. Cisapride up to 2 x 10(-5) M for the GB and 3 x 10(-6) M for the CBD did not modify, whereas, at concentrations higher than 2.8 x 10(-5) M for the GB and 4 x 10(-6) M for the CBD, it antagonized, noncompetitively, the concentration-response curve to exogenously applied acetylcholine. The IC50 values for cisapride on the EC50 of acetylcholine on the GB and the CBD were 9.4 x 10(-5) M and 8.2 x 10(-6) M, respectively. 5. In conclusion, on the guinea pig GB and CBD, low concentrations of cisapride produce a stimulating effect, probably of cholinergic origin, whereas higher concentrations produce a transient stimulating effect, probably of cholinergic origin, followed by a sustained relaxing effect, which may involve both cholinergic and noncholinergic pathways.
Asunto(s)
Conducto Colédoco/efectos de los fármacos , Vesícula Biliar/efectos de los fármacos , Fármacos Gastrointestinales/farmacología , Músculo Liso/efectos de los fármacos , Piperidinas/farmacología , Acetilcolina/farmacología , Animales , Atropina/farmacología , Vías Autónomas/efectos de los fármacos , Cisaprida , Femenino , Cobayas , Técnicas In Vitro , Masculino , Sistema Nervioso Parasimpático/efectos de los fármacos , Parasimpatolíticos/farmacologíaRESUMEN
1. In the present study the effect of flumequine, enoxacin and norfloxacin on the GABA-elicited contractions (EC50 1.10 x 10(-5) M) on the isolated guinea pig ileum was investigated, in a comparative manner. 2. All three fluoroquinolones dose-dependently antagonised the GABA-induced contractions in a non-competitive manner, but no statistical difference in the degree of the antagonism they produced was noted. Besides, they did not influence the ileal cholinergic contractions induced by exogenous acetylcholine. 3. These results suggest that the above fluoroquinolones tested dose-dependently inhibit the contractile effect of GABA on the guinea pig ileum and this inhibition seems to be associated with an antagonistic action of the fluoroquinolones at GABAA-receptors present in the guinea pig ileum.
Asunto(s)
Antiinfecciosos/farmacología , Enoxacino/farmacología , Fluoroquinolonas , Íleon/efectos de los fármacos , Norfloxacino/farmacología , Quinolizinas/farmacología , Ácido gamma-Aminobutírico/farmacología , Animales , Relación Dosis-Respuesta a Droga , Femenino , Cobayas , Masculino , Contracción MuscularRESUMEN
In the present study the effect of ketamine, a dissociative anaesthetic, on the GABA- and on the specific GABAA-agonist muscimol-induced responses of the isolated guinea pig ileum was investigated. GABA as well as muscimol produce a concentration-dependent contractile effect on the duodenum, jejunum and ileum. The sensitivity of the intestinal parts to both the above substances increases from the duodenum to the ileum. Ketamine produces a non-competitive inhibition of the GABA- and muscimol-induced contractions of the ileum, while it does not influence the ileal cholinergic contractions induced by exogenous acetylcholine. These results suggest that ketamine may modify intestinal motility through its antagonistic action at the GABAA-receptor complex.
Asunto(s)
Motilidad Gastrointestinal/efectos de los fármacos , Ketamina/farmacología , Receptores de GABA/efectos de los fármacos , Acetilcolina/farmacología , Animales , Relación Dosis-Respuesta a Droga , Femenino , Cobayas , Íleon/efectos de los fármacos , Técnicas In Vitro , Masculino , Muscimol/farmacología , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
In the present study the effect of ketamine on the contractions caused by propoxur and phoxim on the isolated guinea pig ileum was investigated. Ketamine was found able to inhibit in a concentration-dependent manner the contractile responses of the ileum to propoxur and phoxim, while it did not significantly modify the contractions induced by acetylcholine. Propoxur and phoxim augmented the contractile responses induced by acetylcholine in the presence of acetylcholinesterase. This augmentation was prevented by ketamine, in a concentration-dependent manner. These findings suggest that ketamine inhibits the contractile effect of propoxur and phoxim on the guinea pig ileum and this inhibition seems to be associated with the protection of acetylcholinesterase against the action of these two compounds.
Asunto(s)
Acetilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/farmacología , Ketamina/farmacología , Compuestos Organotiofosforados/farmacología , Propoxur/farmacología , Acetilcolina/farmacología , Animales , Interacciones Farmacológicas , Femenino , Cobayas , Íleon/efectos de los fármacos , Técnicas In Vitro , Masculino , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Factores de TiempoRESUMEN
1. The present study was performed to investigate the effect of ketamine on the contractile responses induced by the H2-receptor antagonist ranitidine and the anticholinesterase agent physostigmine on the isolated guinea pig ileum. 2. The contractile responses induced by ranitidine and physostigmine on the guinea pig ileum were significantly prevented, in a concentration-dependent manner, by ketamine, while the ones induced by acetylcholine were not modified. The contractile responses induced by acetylcholine were inhibited by exogenous acetylcholinesterase. Ranitidine and physostigmine inhibited the above reduction, and this effect was significantly prevented by ketamine in a concentration-dependent manner. 3. These findings show that ketamine inhibits the contractile effect of ranitidine and physostigmine on the guinea pig ileum. This inhibition caused by ketamine seems to be associated with the protection of acetylcholinesterase against the inhibition by ranitidine and physostigmine.
Asunto(s)
Inhibidores de la Colinesterasa/farmacología , Ketamina/farmacología , Fisostigmina/antagonistas & inhibidores , Ranitidina/antagonistas & inhibidores , Acetilcolina/farmacología , Animales , Relación Dosis-Respuesta a Droga , Femenino , Cobayas , Íleon/efectos de los fármacos , Íleon/fisiología , Técnicas In Vitro , Masculino , Contracción Muscular/efectos de los fármacosRESUMEN
The influence of varying concentrations of the H2-receptor antagonists nizatidine and ranitidine on the acetylcholine- and carbachol-induced contractures on the toad rectus abdominis muscle, as well as the possible interaction between the above H2-receptor antagonists and D-tubocurarine were studied. Nizatidine and ranitidine at a concentration of 3.2 x 10(-4) mol l-1 augmented, and at 3.2 x 10(-3) mol l-1 inhibited, the acetylcholine-induced contractures on the toad rectus abdominis muscle, while at concentrations from 3.2 x 10(-4) to 3.2 x 10(-3) mol l-1 they inhibited the carbachol-induced contractures, in a concentration-dependent manner. In addition, nizatidine and ranitidine at a concentration of 3.2 x 10(-4) mol l-1 reversed the D-tubocurarine blocking activity on the acetylcholine-induced contractures, but at a concentration of 3.2 x 10(-3) mol l-1 they augmented it. These findings provide evidence that the above H2-receptor antagonists produce either cholinesterase inhibition or neuromuscular blockade, depending on their concentration. Thus, the D-tubocurarine neuromuscular blocking activity is potentiated at high concentrations of nizatidine and ranitidine, while it is reversed at lower ones.
Asunto(s)
Fármacos Neuromusculares no Despolarizantes/antagonistas & inhibidores , Nizatidina/farmacología , Ranitidina/farmacología , Recto del Abdomen/efectos de los fármacos , Tubocurarina/antagonistas & inhibidores , Acetilcolina/administración & dosificación , Acetilcolina/farmacología , Animales , Bufonidae , Carbacol/administración & dosificación , Carbacol/farmacología , Estado de Descerebración/fisiopatología , Antagonistas de los Receptores H2 de la Histamina/antagonistas & inhibidores , Técnicas In Vitro , Contracción Muscular/efectos de los fármacos , Fármacos Neuromusculares no Despolarizantes/farmacología , Tubocurarina/farmacologíaRESUMEN
1. The effect of erythromycin on the rabbit intestinal smooth muscle was investigated and was compared to that of motilin. 2. Whole isolated segments from the duodenum, jejunum, ileum and ascending colon, as well as strips from the circular and longitudinal smooth muscle of the ascending colon were used. 3. Erythromycin was found to possess a concentration-dependent contractile effect on the above intestinal parts but in different degree of intensity. 4. The order of the sensitivity of the intestinal parts to erythromycin was duodenum = jejunum > ascending colon > ileum. 5. The circular smooth muscle of the ascending colon was found to be more sensitive than the longitudinal smooth muscle. 6. A similar contractile effect, but at lower concentrations, and the same regional specificity were observed with motilin.
Asunto(s)
Eritromicina/farmacología , Intestinos/efectos de los fármacos , Motilina/farmacología , Animales , Colon/efectos de los fármacos , Duodeno/efectos de los fármacos , Femenino , Íleon/efectos de los fármacos , Técnicas In Vitro , Intestinos/fisiología , Yeyuno/efectos de los fármacos , Masculino , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiología , ConejosRESUMEN
The macrolide antimicrobial agents, erythromycin, troleandomycin and tylosin were tested for their effect on isolated whole segments of the rabbit duodenum, jejunum, ileum and ascending colon, as well as on strips of the circular and longitudinal smooth muscle of the ascending colon. The 14-membered macrolides erythromycin and troleandomycin were found to possess a concentration-dependent contractile effect on the intestinal smooth muscle. The order of potency was: erythromycin > troleandomycin. The 16-membered macrolide tylosin was found to have a much weaker potency than erythromycin and troleandomycin. In addition, the circular smooth muscle of the ascending colon was found to be more sensitive to the compounds tested than the longitudinal smooth muscle.