摘要:

The differential effects of haloperidol on dopamine release and its metabolism were investigated in the anteromedial frontal cortex and the caudate putamen using the intracerebral dialysis method in anesthetized rats after single intraperitoneal injections of 0.01, 0.125 and 2 mg/kg haloperidol. The basal levels of dopamine, 3,4-dihydroxyphenyl-acetic acid and homovanillic acid, collected every 20 min from the caudate putamen, were 22, 7.7 × 103 and 5.5 × 103 pg/30 μl, respectively, and were much higher than those from the anteromedial frontal cortex, which were 1.8, 2.6 × 102 and 4.6 × 102 pg/30 μl, respectively. There was a clear difference in the time-response curve of dopamine release between the two brain regions after the injection of 0.125 mg/kg haloperidol, but no difference after the administration of the other doses. The measurements of 3,4-dihydroxyphenylacetic acid and homovanillic acid showed a difference between the two brain structures after the injection of 0.01 mg/kg haloperidol, but did not show such a clear difference after injection of the other doses. These findings suggest that there is a difference between the anteromedial frontal cortex and the caudate putamen with respect to the regulating mechanism of dopamine release and its metab

ISSN:0031-7012    

DOI:10.1159/000138761

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The effects of morphine on memory have been shown to be dependent on the strain of animal used and on the experimental parameters. Memory was assessed in a passive avoidance task using Swiss albino (ICRC) mice. Morphine at doses of 1 3 and 10 mg kg–1 was administered immediately after foot shock (memory retention) or 23.5 h after foot shock (memory retrieval). Retest step-down latencies measured 24 h later showed that morphine did not affect memory retention but dose-dependently impaired retrieval of memory. Administration of naloxone 0.1 mg kg–1 antagonised the effects of morphine and impaired memory retention. Propranolol 0.3 mg kg–1 along with morphine 3 mg kg–1 impaired memory retention only while haloperidol 0.1 mg kg–1 improved the impairment of memory retrieval caused by morphine 3 mg kg–1. Glucose did not alter the effects of morphine on memory. There was no per se effect of morphine, naloxone, propranolol, glucose and haloperidol on memory at the doses used. The effect of morphine on memory retention is mediated by opioid mechanisms; however, adrenergic and dopaminergic mechanisms possibly modulate retention and retrieval of memory, r

ISSN:0031-7012    

DOI:10.1159/000138762

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Rats of the Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) strains were placed on a 4% NaCl diet and blood pressures were monitored. Chronic subcutaneous infusion of L-5-hydroxytryptophan (L-5-HTP, 12.6 mg/day) by osmotic minipumps significantly decreased the elevated systolic blood pressure of DS rats on a 4% NaCl diet. Blood pressures of DR rats were unaffected by treatment with L-5-HTP. Cardiac hypertrophy was associated with Dahl salt-induced hypertension. However, treatment with L-5-HTP failed to reduce the weight of the heart significantly. These results suggest that chronic administration of L-5-HTP was effective in reducing the elevated blood pressure in the DS model. The specific mechanisms by which L-5-HTP reduces the elevated blood pressure in DS rats is not clear and remains for further study.

ISSN:0031-7012    

DOI:10.1159/000138763

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

These studies evaluated the antimuscarinic activity of bornaprine hydrochloride, a synthetic anticholinergic drug utilized in the treatment of parkinsonism. Several of its metabolites were also evaluated. Biological activity was assessed by the ability of the compounds to inhibit the negative inotropic response to carbachol in the isolated left atrium of the rat. Bornaprine showed a pA2 value (concentration required to reduce the agonist response by 50%) of 7.27 ± 0.21. The exo and endo epimers were approximately equipotent in this regard. One metabolite, the 5-hydroxyl, showed similar activity to the parent compound, whereas 2 other hydroxylated metabolites showed much less effect

ISSN:0031-7012    

DOI:10.1159/000138764

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Glucuronidation and sulfation of 1-naphthol, 7-hydroxycoumarin, 4-nitrocatechol and phenolphthalein were studied in rabbit lung and liver. Pulmonary UDP-glucuronyltransferase and sulfotransferase activities in subcellular fractions were approximately 20–50% of those determined in the liver. Ethanol did not markedly induce these enzymes in either tissue. Glucuronidation and sulfation of 1-naphthol and 7-hydroxycoumarin were also studied in the isolated perfused rabbit lung as an intact cell model. Neither glucuronidation nor sulfation of 1-naphthol was observed. The absence of conjugate formation was due neither to the presence of β-glucuronidase and/or sulfatase, nor to alternative biotransformation pathways. About 35% of the initial 7-hydroxycoumarin was conjugated, the majority being sulfate conjugate (14.4 nmol/h) with only minor amounts (0.12%) of the glucuronide. These results indicate the importance of studying both whole organ and in vitro metaboli

ISSN:0031-7012    

DOI:10.1159/000138765

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Domestic pigs received single intravenous and oral doses of lorazepam or clonazepam (1 mg/kg), benzodiazepine derivatives biotransformed by glucuronide conjugation and nitroreduction, respectively. Blood samples were simultaneously drawn from portal venous and systemic venous sampling sites during 8 h after dosage. After intravenous dosage with either drug, the area under the serum concentration curve (AUC) for the intact drug, as well as for the principal metabolites (lorazepam glucuronide and 7-aminoclonazepam, respectively), was nearly identical between portal and systemic serum. After oral dosage, absolute systemic availability (relative to intravenous administration) of both lorazepam and clonazepam was incomplete (mean values: 29 and 49%, respectively); however, metabolite levels were also correspondingly lower between oral and intravenous dosages. First-pass hepatic extraction also occurred for both drugs, with mean systemic/portal AUC ratios of 0.60 for lorazepam and 0.74 for clonazepam. Pretreatment with neomycin (1.0 g) had a minimal effect on portal or systemic AUC for intact clonazepam after oral dosage, but 7-aminoclonazepam concentrations were reduced by neomycin pretreatment. Thus incomplete absorption, together with first-pass hepatic biotransformation, appears to explain the incomplete systemic availability of orally administered lorazepam or clonazepam. Biotransformation within the gastrointestinal tract or during absorption through the gastrointestinal mucosa contributes minimally.

ISSN:0031-7012    

DOI:10.1159/000138766

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The present experiments examined the protective effect of the nitrofuran drugs, furazolidone (FZ) and nitrofurazone (NF), on duodenal ulceration induced by cysteamine or indometacin in rats. FZ at oral doses of 25, 50 or 100 mg/kg for 2 consecutive days significantly reduced, in a dose-dependent manner, the incidence and extent of cysteamine-induced ulceration. However, oral NF (100 mg/kg) given for 2 consecutive days had no significant effect on duodenal ulceration. The duodenal mucus content of rats was not significantly affected by either FZ or cysteamine treatments. FZ at an oral dose of 100 mg/kg for 2 consecutive days significantly reduced the incidence and extent of indometacin-induced ulceration. Smaller doses of 25 or 50 mg/kg had no significant effects.

ISSN:0031-7012    

DOI:10.1159/000138767

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

In anesthetized rabbits, we can induce a significant degree of spontaneous activity in the urinary bladder by placing a ligature around the proximal portion of the external urethra. Previous studies characterized the activity as primarily reflex in nature, since intravesical hexamethonium selectively inhibited the hyperreflexia. In this current study we determined the effect of intravesical administration of a variety of compounds to inhibit the induced hyperreflexia. The following agents were tested at concentrations of 1, 10, 100 and 500 μmol/l (intravesically): verapamil, cromakalim, nifedipine, diltiazem, and atropine; lidocaine was tested in 0.05, 0.5 and 5% solutions. The results are summarized as follows: (1) Lidocaine was the most effective agent tested, virtually eliminating both the amplitude and frequency of the spontaneous activity at the lowest concentration (0.5%). (2) Verapamil and nifedipine were somewhat more potent than cromakalim and diltiazem. Atropine sulfate was the least potent, inhibiting both the amplitude and frequency of the hyperreflexia by less than 50% at 500 μmol/l. (3) In all cases, the amplitude of the spontaneous activity was inhibited to a significantly greater degree than the frequency of the spontaneous activity. (4) In general, there was no effect of any of the agents on mean arterial pressure at 1 or 10 μmol/l. At 100 and 500 μmol/l, all agents except for lidocaine and cromakalim decreased arterial pressure. These two agents produced no consistent fall in blood pressure at any concentration. In conclusion, the acute hyperreflexic (rabbit) preparation provides a highly reproducible and consistent model for the study of the effect of drugs on hyperreflexia. The data presented in this report would indicate that the intravesical administration of antispasmodic (and other) agents might provide a useful method of treatment for this condit

ISSN:0031-7012    

DOI:10.1159/000138768

出版商:S. Karger AG    

年代:1991

数据来源: Karger