ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00220.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Kaya, F., Van Duin, C.T.M.&Van Miert, A.S.J.P.A.M. Food intake and rumen motility in dwarf goats. Effects of some dopamine receptor agonists.J. vet. PharmacolTherap,17, 120–126.In ruminants, the dopaminergic regulation of feeding behaviour has not been investigated. Therefore, the effects of dopamine receptor agonists and antagonists on food intake and forestomach motility were studied in dwarf goats Goats treated i.v. with bromocriptine (1 μg or 2.5 μg/kg body wt/min during 10 min) ate less food than when treated with saline. This inhibitory effect on food intake could not be prevented by the peripheral dopamine receptor antagonist domperidone (0.5 mg/kg body wt i.v.). In contrast, dopamine (i.v. 20 μg/kg body wt/min during 15 min), levodopa (i.v. 40 μg/kg body weight during 10 min), apomorphine (i.v. 2 μg/kg body wt/min during 10 min) and lisuride (i.v. 0.2 μg/kg body wt/min during 15 min and 0.5 μg/kg body wt during 10 min) failed to modify food intake. Given in association with benserazide, a decarboxylase inhibitor (i.v. 20 μg/kg body wt/min during 10 min), levodopa was still inactive as an anorectie agent. Levopoda, bromocriptine and lisuride administered at similar dose rates to those which were used in the food intake experiments, induced some clinical signs including inhibition of forestomach contractions. The inhibition of rumen contractions induced by these drugs was completely antagonized by domperidone pretreatment. These results, together with earlierin vivoand invitroobservations, suggest that the inhibitory effects of dopamine receptor agonists on forestomach contractions are due to interactions with peripheral dopaminergic receptors. The change in smooth muscle tension, which leads to a change in the signals transmitted via vagal afferents to the central nervous system, probably does not modify feeding behaviour in dwarf goats. Furthermore, i.v. infusion of lisuride induced rumination when the inhibition of the forestomach contractions was prevented by domperidone; this effect may involve α2‐adrenocepto

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00221.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Simultaneous pharmacokinetic‐pharmacodynamic (PK‐PD) models of meperidine in Soats were established by utilizing the P3wave of the cerebral evoked potentials as an analgesic measurement. An effect compartment linked to the central compartment was postulated in the models. The hypothetical drug amount in the effect compartment was related to the observed analgesia through the Hill equation. After intramuscular (i. m.,n= 16) and intravenous (i. v.,n= 13) dosing (5 mg/kg), the elimination rate constants of meperidine in the effect compartment (KeO) were 0.3744 ± 0.2546 and 0.1123 ± 0.0428 min‐1, drug concentrations in the effect compartment generating half maximal analgesia (EC(50)) were 0.70 ± 0.33 and 0.41 ± 0.26 μg/ml, the maximal effects (Emax) were 89.63 ± 15.63 and 85.92 ± 9.64%, and the Hill coefficients (S) were 2.61 ± 1.21 and 2.37 ± 1.15, respectively.KeOand EC(50)with i.m. dosing were significantly greater than with i.v. injection. However, administration route had no influence on S, Emaxand the total amount of effect (AUE). The predicted peak effect (Emax^) of 64.44 ± 14.64 and 66.02 ± 11.51% were achieved at 14.7 ± 7.4 and 8.5 ± 2.2 min after i.m. and i.v. dosing, respectively. Peak analgesia appeared much later than peak plasma concentration, but simultaneously with peak CSF level both after i.m. and i.v. dosing. An obvious hysteresis was demonstrated between plasma concentration and analgesic effect. This study demonstrates that meperidine analgesia can be predicted using a PK‐PD model, but not by PK data alone. Both i.m. and i.v. administration routes were evaluated kinetic

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00222.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The bioavailability of levamisole in rabbits was determined after subcutaneous and oral administration at three dose levels of 12.5, 16.0 and 20.0 mg/kg. After non‐compartmental analysis the mean values obtained were:Cmax=3.54, 4.51 and 5.39 μg/ml;tmax= 12.0, 22.0 and 20.0 min;F= 134.8, 105.4 and 124.1% after subcutaneous administration for each dose, respectively, andCmax= 0.71, 1.32 and 1.77 μg/ml;tmax= 46.0, 96.0 and 84.0 min;F= 53.0, 62.0 and 80.7% after oral administration. The extent and rate of absorption from the two routes differed significantly, except fortmaxat the 12.5 mg/kg dose. After compartmental analysis the pharmacokinetics of levamisole was characteristic of a two‐compartment open model in 13 rabbits and of a one‐compartment open model in two rabbits after subcutaneous administration, while it was two compartmental in nine and one compartmental in six rabbits after oral administration. The kavalues were 0.321, 0.145 and 0.145 min‐1after subcutaneous administration and 0.054, 0.023 and 0.027 min1after oral administration. There were no significant differences between the values ofCmax,tmaxandAUCcalculated by compartmental and non‐compartment

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00223.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The bioavailability of metoclopramide was investigated in three steers following administration of 8 mg/kg by the oral, abomasal (cannula), and intravenous routes, using a Latin square design. The mean (± SD) oral and abomasal bioavailabilitles were 51.3 ± 30.7% and 76.2 ± 15.5%, respectively. The mean value for clearance (C1) was 20.1 ± 5.9 ml/min and the volume of distribution (Vd) was 0.51 ± 0.19 1/kg. Additionalpharmacokmetic parameters for metoclopramide were determined following intravenous administration to seven cows. A predominate two‐compartment model of distribution was found in six cows with at1/2αharmonic mean of 24.2 min and a range of 11.2–72.4 min, at1/2βharmonic mean of 53.1 min and a range of 31.1–134.1 min, aClof 42.2 ± 8.7 ml/min, and aVdof 2.1 ± 0.8 1/kg. To better define the relationship between metoclopramide concentration and release of prolactin, a treatment‐by‐subjects infusion study was conducted in which four different loading doses followed by constant infusion were used. A steady‐state metoclopramide concentration (MCPss) of 8.8 ± 2.6 ng/ml was associated with a three‐fold elevation of prolactin to a mean value of 12.1 ± 3.1 ng/ml in six yearling steers. Steady state serum prolactin concentrations (PRLss) did not rise significantly above 23.3 ± 6.9 ng/ml, even whenMCPssreached a concentration of 518.5 ±151.2 ng/ml. The short half‐life, moderateVd, low minimum pharmacologically effective concentration, and rapidC1found for metoclopramide in cattle in this study, suggest that a continuous release device could potentially be useful in the application of this drug in the prevention and t

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00224.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The motor responses of the jejunum and colon to stimulation of α2‐adrenoceptors by medetomidine and clonidine were investigated in four dogs. In fasting dogs, medetomidine, at a dose rate of 30 μg/kg i.v., disrupted the migrating myoelectric complex (MMC) pattern of the small intestine for about 2 h. Similar, but shorter‐lasting effects were also induced by clonidine (30 μg/kg i.v.) on the jejunum. The administration of α2‐agonists inhibited colonic motility in fasting dogs, although medetomidine‐induced inhibition was preceded by a short period of increased muscle tone. All these effects were reversed by the α2‐antagonists atipamezole (0.15 mg/kg i.v.) and yohimbine (0.20 mg/kg i.v.). In fed dogs, medetomidine (30 μg/kg i.v.) induced a strong increase of the tone on the proximal colon, while the activity of the medium and distal colon was completely suppressed. Yohimbine (0.50 mg/kg i.v.) immediately restored the activity of the colon and induced a propagated giant contraction and defaecation by the animal. These data confirm the importance of a2‐adrenergic receptors in the control of intestinal and colonic mo

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00225.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00226.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00227.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1994.tb00228.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY