摘要:

AbstractThe development and maintenance of the normal functional integrity of the mammalian central nervous system is under the influence of a number of growth and trophic factors. One such growth factor, epidermal growth factor, has been detected in the mammalian brain and found to be associated with various brain regions and cell types. This small ubiquitous polypeptide can influence the proliferation, Metabolism, and differentiation of both glia and neurons in the central nervous system. We discuss the effects of epidermal growth factor on glial and neuronal cell function in an attempt to understand its role in development and maintenance of normal brain integrity. In addition, we review its possible implications in several pathological states in the central nervous system and speculate on therapeutic applications for this growth factor. © 1992 Wiley‐Liss, I

ISSN:0272-4391    

DOI:10.1002/ddr.430260202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractMotor activity effects of haloperidol, risperidone, and ocaperidone were studied in rats challenged with amphetamine. At a low dose of amphetamine, the compounds were about equipotent in reducing amphetamine‐induced hyperactivity to normal values (lowest ED50s: 0.015–0.023 mg/kg). Haloperidol completely blocked motility at a slightly higher dose (0.14 mg/kg). In contrast, much higher doses of risperidone and ocaperidone were required for complete blockade of motility (ED50s: 2.0 and 1.7 mg/kg, respectively). With increasing dose of amphetamine, risperidone became considerably less potent than haloperidol in reducing hyperactivity; ocaperidone remained at least as potent as haloperidol in this respect. Moreover, risperidone lost, while ocaperidone maintained, its high margin towards complete blockade of motility. The compounds were also equipotent (lowest ED50s: 0.0075–0.0089 mg/kg) in reversing amphetamine‐induced behavioral withdrawal (stationary stereotypy) to more environment directed behavior (active exploration). However, this ‘disinhibitory’ effect was maintained over a much wider dose range with risperidone than with haloperidol and ocaperidone. The observed differences in interaction with amphetamine are presumably related to relative serotonin 5HT2/dopamine D2antagonistic activity and suggest important differences in therapeutic profile and side‐effect liability of the compounds. The implications for distinct clinical applications of the compounds are discussed: risperidone might be the drug of choice for maintenance therapy of chronic schizophrenics, especially for patients with mild positive symptoms and type II patients with predominant negative symptoms and ocaperidone for therapeutic treatment of the pronounced positive symptoms in acute schizophrenia or during exacerbations of chronic schizophrenia. © 1992 W

ISSN:0272-4391    

DOI:10.1002/ddr.430260203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe effects of S 9977‐2, a new compound which belongs to the trimethylxanthine family and has shown in vivo promnesic activity and in vitro acetylcholinesterase activities inhibition, were studied on the guinea pig isolated trachea and on human isolated bronchi. On the guinea pig isolated trachea, S 9977‐2 in concentrations of 10−7–10−4M potentiated the contractile effect of acetylcholine. The potency of acetylcholine was increased 3.39, 4.26, 9.54, and 13.18 fold with concentrations of 10−7, 10−6, 10−5, and 10−4M, respectively. The maximum effect of acetylcholine was not modified. S 9977‐2 did not potentiate the effects of carbachol or pilocarpine. Under similar conditions, eserine (10−8and 10−6M) and tacrine (10−8–10−6M) also potentiated the effects of acetylcholine. The potentiating effect of these two substances was stronger than that of S 9977‐2, with a 44.7 fold increase for eserine (10−7M) and a 64.6 fold increase for tacrine (10−6M). However, both eserine and tacrine had a contractile effect of their own on the guinea pig isolated trachea, whereas S 9977‐2 had no such effect. On the human isolated bronchus, S 9977‐2 at a concentration of 10−5M produced a 19.1 fold increase of acetylcholine effects. On the guinea pig isolated trachea, the effects of S 9977‐2 vs. acetylcholine were not modified by epithelium removal. They were increased by pretreatment with indomethacin 10−6M. In very high concentrations (10−4and/or 10−3M), S 9977‐2 reduced the effects of histamine and those of serotonin on the guinea pig isolated trachea. S 9977‐2 had no effect on the contractile action of potassium chloride or on the relaxant action of adenosine. The results suggest that in the airway smooth muscle S 9977‐2 partially inhibits acetylcholinesterase and/o

ISSN:0272-4391    

DOI:10.1002/ddr.430260204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe present study was undertaken in order to examine the effects of the potassium channel activator BRL38227 and of aminophylline on hypokalaemia, cardiac stimulation (increased heart rate and contractility, dQ/dt), and electrocardiogram (ECG) changes induced by the β2‐adrenoceptor agonist, salbutamol in the anaesthetised cat. Salbutamol (1.25 μg.kg−1min−1), but not BRL38227 (0.1–1.0 μg.kg−1min−1), infusion elicited a marked hypokalaemia (plasma K+>2.5 mmolliter−1). This dose of salbutamol also elicited an immediate cardiac stimulation which appeared to be maximal and changes in ECG were evident as a reduction in QTc interval (20%) and T‐wave height (80%). Cardiac stimulation following either BRL38227 or aminophylline was more gradual in onset, the maximum response being about 50–80% of the salbutamol effect. No ECG changes were observed in cats receiving BRL38227 whilst T‐wave amplitude was reduced (50–60%) following aminophylline. Combination of salbutamol with aminophylline resulted in a greater degree of hypokalaemia, cardiac stimulation, and T‐wave depression. The salbutamol‐induced reduction in QTc was converted to a slight prolongation after infusion for 75 min. The ECG changes observed were not indicative of arrhythmia. Conversely, BRL38227 had no effect on salbutamol‐induced hypokalaemia, cardiac stimulation, or T‐wave depression, though the degree of QTc interval shortening was reduced. When BRL38227 was administered in conjunction with aminophylline, plasma potassium and QTc were unchanged. Depression of T‐wave amplitude by aminophylline was slightly reduced in the combination group. Effects on heart rate and dQ/dt were similar to those seen for BRL38227 alone. Salbutamol‐induced hypokalaemia was reversed by the nonselective β‐adrenoceptor antagonist, propranolol, but not by the β1‐adrenoceptor selective antagonist, atenolol, confirming a β2‐adrenoceptor selective effect. Cardiac stimulation was reversed by both propranolol and atenolol. In conclusion, salbutamol‐induced hypokalaemia, cardiac stimulation, and ECG changes, as well as the additive effect of aminophylline, were demonstrated in the anaesthetised cat, but were unchanged by BRL38227. Furthermore, combination of BRL38227 with aminophylline did not result in any adverse effects on the parameters measured. Thus, on the basis of these results in the cat, combination of BRL38227 with the bronchodilator drugs, salbutamol or aminophylline, would not be expected to exacerbate the cardiovascular

ISSN:0272-4391    

DOI:10.1002/ddr.430260205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractWe examined the cerebral protective effects of AE0047 employing cerebral ischemia models. In the bilateral carotid arterial occlusion model (BCAO) employing spontaneously hypertensive rats (SHRs), oral administration of AE0047 (0.1–0.3 mg/kg) or nicardipine (3 mg/kg) improved the neurological symptoms by 2 hr after the BCAO procedure and energy metabolite changes 30 min after the BCAO procedure. AE0047 was significantly effective in these 2 models at one‐tenth the dosage of nicardipine. Dihydroergotoxine completely protected in an adrenaline‐induced lethality model. AE0047 also showed a protective action in this model and is considered to have an α‐adrenergic blocking action similar to dihydroergotoxine. In the KCN‐induced abnormal behavior (the coma and the disappearance of searching behavior) and death models, protective effects were observed in the AE0047 group, but not in the nicardipine group. Protective action was marked even 2–4 hr after AE0047 administration. Dihydroergotoxine also shortened the duration of coma and prolonged the survival time, but had no effect on mortality. From these results, it is suggested that the α‐adrenergic blocking action of AE0047 participates in the antihypertensive action. The protective effects of AE0047 were most striking at 2 and 4 hr after AE0047 administration. © 1992

ISSN:0272-4391    

DOI:10.1002/ddr.430260206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractDose (1.5–12 mg/kg p.o. × 7) dependent choleretic, anticholestatic, and hepatoprotective activity in rat was observed with N‐demethyl ricinine isolated from the leaves ofRicinus communisLinn. The anticholestatic and hepatoprotective activity was seen against paracetamol‐induced hepatic damage. The choleretic and anticholestatic activity was evidenced by an increase in the volume of bile and its contents. The hepatoprotective effect was evaluated by an increase in the percent viability of hepatocytes (ex vivo) and by the reversal of altered enzymatic levels (glutamic oxaloacetic transaminase [GOT], glutamic pyruvic transaminase [GPT], and alkaline phosphatase) towards normal. The compound showed more potent activity than silymarin, a known hepatoprotective

ISSN:0272-4391    

DOI:10.1002/ddr.430260207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe purpose of the present study was to assess the potential interaction between clozapine, an atypical antipsychotic recently approved for clinical use in the United States and nicotine. Male Sprague‐Dawley rats were trained to discriminate nicotine or clozapine in a standard two‐lever operant drug discrimination procedure. Rats were tested for generalization to nicotine and clozapine, and the interactions produced by combining various doses of nicotine and clozapine were evaluated. Results suggest that nicotine does not interact with the discriminative stimulus effects of clozapine. Thus, patients who smoke while receiving clozapine therapy may not experience the decreased antipsychotic effectiveness which is common in patients who smoke while receiving treatment with typical antipsychotic compounds. © 1992 Wiley‐Lis

ISSN:0272-4391    

DOI:10.1002/ddr.430260208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe diuretic and the antihypertensive actions of torasemide were examined in renal and genetic hypertensive rats and compared to the effects of furosemide. Oral administration of torasemide (1 and 3 mg/kg) elicited a dose‐dependent increase in the excretion of urine and electrolytes and elevated the urinary Na/K ratio in both renal and genetic hypertensive rats. Torasemide and furosemide had a similar maximum diuretic effect in the normotensive Wistar rat and the spontaneously hypertensive rat (SHR). However, the diuretic activity of furosemide was weaker in the renal hypertensive rat (RHR). Torasemide showed approximately 30 times greater diuretic potency than furosemide. Torasemide and furosemide demonstrated hypotensive action in hypertensive rat models, but not in the normotensive Wistar rat. Especially in the RHR, torasemide exhibited a more potent hypotensive action than furosemide. These results show that the diuretic and antihypertensive activities of torasemide are effective in various rat models of hypertension, while the diuretic activity of furosemide is weak in certain hypertensive rat models. © 1992 Wiley‐Liss,

ISSN:0272-4391    

DOI:10.1002/ddr.430260209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

ISSN:0272-4391    

DOI:10.1002/ddr.430260210

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

ISSN:0272-4391    

DOI:10.1002/ddr.430260201

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY