摘要:

The effect of chronic administration of morphine to Sprague-Dawley rats on the binding of dopamine receptor agonist, 3H-N-n-propylnorapomorphine (3H-NPA) to striatal membranes was determined. For chronic administration of morphine, rats were implanted subcutaneously with four morphine pellets (each containing 75 mg of morphine free base) during a 3-day period. Placebo pellet-implanted rats served as controls. Two experimental protocols were followed. In one, the rats were sacrificed 70 h after the implantation of first pellet and in the other, the pellets were removed and the animals were sacrificed 24 h later, and the binding of 3H-NPA was determined. Rats receiving morphine showed no difference in the total number of binding sites (Bmax value) but there was a decrease in the apparent dissociation constant (Kd value) compared with placebo controls. Moreover, such a decrease in Kd in morphine-treated rats persisted even 24 h after removal of morphine pellets. The effect of prolyl-leucyl-glycinamide (MIF; 2 mg/kg), which has been shown to inhibit the development of tolerance to and dependence on morphine, on the changes in the binding of 3H-NPA induced by the implantation of morphine pellets was also determined. MIF antagonized the decreases in Kd values induced by the administration of morphine. However, when administered chronically by itself, MIF had no effect on either the Bmax or Kd values of 3H-NPA. It is concluded that the chronic administration of morphine is associated with enhanced activity of dopamine receptors in the central nervous system as revealed by lowering of the Kd value of the agonist, NPA. This effect was reversed by MIF, an agent known to inhibit the development of tolerance to and dependence on morphine.

ISSN:0031-7012    

DOI:10.1159/000138128

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The antagonistic action of D-baclofen at baclofen receptors mediating antinociception in the spinal cord was examined. Drugs were administered intrathecally to rats and effects on nociceptive threshold evaluated in the tail flick test. L-Baclofen, D-baclofen and the racemate produced dose-related increases in tail flick latency, with L-baclofen being twice as potent as the racemate and approximately 100 times more potent than D-baclofen. When D-baclofen was injected 15 min prior to L-baclofen, it produced a dose-related inhibition of the effect of L-baclofen. Concomitant administration produced a more ambiguous effect. Antagonism appeared specific for baclofen receptors because analogues with full and partial agonist activity as well as an agonist dose of D-baclofen, but not morphine or noradrenaline, were inhibited by pretreatment with D-baclofen. γ-Aminobutyric acid (GABA) did not increase tail flick latency either alone or following pretreatment with an uptake inhibitor or a GABA-transaminase inhibitor. Antinociception produced by intrathecal administration of Baclofen appears to result from activation of a receptor which is stereoselective for the L-isomer and can be blocked by D-baclofen in doses which have initial agonist activity. This receptor may not be a GABA subtype because GABA does not mimic the effect of baclofen and the rank order of potency of analogues differs from established GABAB systems

ISSN:0031-7012    

DOI:10.1159/000138129

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

Various new butyridenyl-2-hydroxybenzylidenyl-1,3-thiazolidinones were synthesized and characterized by elemental analyses, IR and PMR spectral data. The compounds were evaluated for their ability to afford protection against inflammation by carrageenin-induced oedema and cotton pellet implantation in albino rats of either sex. The active derivatives of the present series were also tested for their analgesic activity against aconitine-induced writhing in albino mice and ulcerogenic activity in albino rats. The toxicity of the compounds was reflected by determination of their approximate LD50 in albino mice. An attempt has also been made to correlate their structure-activity relationship.

ISSN:0031-7012    

DOI:10.1159/000138130

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

In order to determine if the calcium blocker diltiazem could alter excitation-secretion coupling in vascular sympathetic nerves, superfused rabbit pulmonary arterial strips were preincubated with 3H-norepinephrine and stimulated electrically (2–8 Hz) and by KCl (60 mM). Diltiazem significantly inhibited tension development with 4 Hz (1.5 × 10–5 M) and 8 Hz (1.5 × 10–6, 1.5 × 10–5M) stimuli, but only at 1.5 × 10–5M did diltiazem inhibit the 3H overflow evoked by an 8-Hz stimulus. No inhibition of 3H overflow was noted with the 2 and 4 Hz stimuli. With an 8-Hz stimulus the inhibition of tension development (45.4%) by diltiazem (1.5 × 10–5M) was significantly greater than the inhibition of 3H overflow (33.8%). A similar relationship was noted with 60 mM KCl stimulation. These data suggest that excitation-secretion coupling in vascular sympathetic nerves can be inhibi

ISSN:0031-7012    

DOI:10.1159/000138131

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The regulatory action exerted on receptors by acebutolol, a cardioselective β-blocker containing intrinsic sympathomimetic activity, has been investigated. β-Adrenoceptor affinity and density of human mononuclear leukocytes were assayed in hypertensive patients before and after treatment with 400 mg/day acebutolol. While receptor affinity showed no changes between pre- and post-treatment values, a statistically significant decrease has been demonstrated in receptor density following treatment. Blood pressure and heart rate were also measured in order to test the efficacy of the administered drug. All these parameters showed a fall in the post-treatment values. It is concluded that the partial agonist acebutolol, in spite of the fact that it acts clinically as a β-blocker, has the regulatory mechanism characteristic of agonis

ISSN:0031-7012    

DOI:10.1159/000138132

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

To determine the effect of dialysate osmolarity on peritoneal dialysis drug transfer, peritoneal dialysis clearances of theophylline, phenobarbital, and tobramycin were determined in 10 rabbits using dialysate containing 1.5 and 4.25% glucose. Urea and creatinine clearances were also obtained for comparison. Under similar dialysis conditions, the peritoneal clearances of the three drugs remained unchanged for the two types of dialysate. In contrast, the peritoneal clearances of urea and creatinine were significantly higher with the use of 4.25 % glucose dialysate (p < 0.001). Thus, peritoneal dialysis clearances of theophylline, phenobarbital and tobramycin are not significantly affected by hypertonicity-induced ultrafiltration during acute peritioneal dialysis.

ISSN:0031-7012    

DOI:10.1159/000138133

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The cytochromes P-450 of the mixed function oxidase system metabolize a wide variety of endogenous compounds to either nontoxic products or toxic metabolites. A number of natural products, such as flavonoids, influence this metabolism. Exposure to these compounds may therefore be a factor in animal and human responsiveness to cytochrome P-450 substrates. We have examined the effect of the pterocarpan medicarpin on the cytochrome P-450-dependent aryl hydrocarbon hydroxylase (AHH) and ethoxycoumarin deethylase (ECD) activities of rat liver microsomes. Medicarpin and maackiain and two of their biosynthetic precursors inhibit the constitutive and phenobarbital (PB)-induced types of AHH, but have little effect on the 3-methylcholanthrene (MC)-induced type of AHH. This is in contrast to the effect of the commonly used cytochrome P-450 inhibitor 7,8-benzoflavone, which inhibits the hepatic AHH of MC-treated rats and has no effects on the AHH of control or PB-treated rats. However, medicarpin inhibited the constitutive as well as the PB- and MC-induced ECD. The specific modulatory effect as well as its relative availability suggests the utility of medicarpin as a probe for different forms of cytochrome P-450 in animal tissues.

ISSN:0031-7012    

DOI:10.1159/000138134

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

Mice were either pretreated with naloxone (10 mg/kg i.p.) and then injected with a hypnotic, or given a similar dose of naloxone simultaneously with a hypnotic (combination treatment). Neither the naloxone pretreatment nor the combination treatment changed the time of on-set or the sleeping duration of urethane, chloral hydrate or ketamine. However, the naloxone pretreatment markedly decreased the on-set time and prolonged the sleeping duration of phenobarbitone and barbitone; naloxone in combination prolonged the sleeping duration of pentobarbitone, phenoabarbitone and barbitone.

ISSN:0031-7012    

DOI:10.1159/000138135

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The effect of sucralfate treatment (3 g daily for 6 weeks) on gastric HCO3 secretion was investigated in 15 duodenal ulcer patients. After treatment a highly significant (p < 0.01) increase in gastric bicarbonate output was found. It is suggested that the mode of action of sucralfate includes stimulation of gastric alkaline secretion.

ISSN:0031-7012    

DOI:10.1159/000138136

出版商:S. Karger AG    

年代:1985

数据来源: Karger