摘要:

AbstractStudies of the effects of small peptides (<10,000 Da), i.e., fragments of naturally occurring hormones (e.g., adrenocorticotrophic hormones [ACTH]: α‐melanocyte‐stimulating hormone [α‐MSH]), hypophysiotrophic factors (e.g., growth hormone‐releasing hormone [GHRH], thyrotropin‐releasing hormone [TRH]), other growth factors, and synthetic compounds on peripheral and CNS neuronal regeneration and behavior have been reviewed and analyzed. It seems apparent that certain hormonal fragments, growth factors, and some synthetic compounds (e.g., the ACTH/α‐MSH analogue Org 2766) can enhance peripheral, and possibly CNS, nerve regeneration. Further study of newer peptide‐analogues with increased potency, longer duration of activity, and greater selectivity of action might lead to the development of therapies for certain types of nerve injury and for neurodegene

ISSN:0272-4391    

DOI:10.1002/ddr.430110202

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

年代:1987

数据来源: WILEY

摘要:

AbstractWhen the parameters of taste aversion conditioning and testing have been appropriately adjusted, benzodiazepines and barbiturates will markedly antagonize the expression of moderate taste aversions in rats. We call this the taste aversion conflict model of anxiety. In the present study, we investigate whether buspirone HCl (buspirone; p.o. and i.p.) is active in the taste aversion conflict model and whether buspirone will also increase unsuppressed saccharin (SACC) intake. We also investigated the effects of imipramine, desipramine, phenelzine sulfate, chlorpromazine, scopolamine and d‐amphetamine sulfate in the taste aversion conflict model. To assess the possible effects of buspirone on the GABA‐benzodiazepine supramolecular receptor complex, we compared buspirone with certain benzodiazepines, meprobamate and sodium phenobarbital on the antagonism of pentylenetetrazol‐induced lethality in mice. Unlike benzodiazepines, meprobamate and phenobarbital, buspirone did not antagonize pentylenetetrazol‐induced lethality. However, like those other anxiolytics, buspirone markedly antagonized the expression of conditioned taste aversion. All nonanxiolytic drugs tested had either no effect or very slight effects on the expression of conditioned taste aversion. These results suggest that the taste aversion conflict model is sensitive to novel anxiolytics and that it is selective for drugs clinically effective in the treatment of generalized anxiety disorders

ISSN:0272-4391    

DOI:10.1002/ddr.430110203

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

年代:1987

数据来源: WILEY

摘要:

AbstractDiscriminated escape behavior of mice in a T‐maze was evaluated as a model for investigation of drug effects upon memory. All studies involved discriminated escape training trials on which footshock offset occurred following a correct goal‐arm choice. Memory was assessed in retention tests that involved either reversal or relearning of the previously trained goal choice. Analyses of discriminated escape acquisition and training‐retention interval were performed to identify parameters yielding either optimal or poor retention. Parameters yielding poor retention in untreated mice were used in studies involving drugs expected to improve retention. Pretraining treatment of mice with either physostigmine (0.08 mg/kg) or HydergineTM(0.64 mg/kg) yielded improved retention scores when training was minimal (a criterion of two consecutive correct choices) and the retention interval was long (168 hr). The effects of scopolamine (0.64 mg/kg) upon memory were assessed in the context of a short retention interval (24 hr) and more complete training (three consecutive correct choices), parameters yielding optimal retention in saline‐treated mice. Scopolamine yielded poorer 24‐hr retention performance when present during training, retention, or at both times. Overall, the results indicate that the discriminated escape procedures described are potentially useful for detection and analysis of pharmacologic modifications of memory

ISSN:0272-4391    

DOI:10.1002/ddr.430110204

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

年代:1987

数据来源: WILEY

摘要:

AbstractResults from a series of standardized tests in rodents were used to describe the general neuropharmacology of vinpocetine, a putative cerebral activator. Vinpocetine was tested at doses ranging from 5 to 100 mg/kg p.o.; these doses are greater that its behaviorally active doses (i.e., 1 to 5 mg/kg p.o.). Vinpocetine did not impair rotarod performance or produce ataxia in mice. Vinpocetine antagonized electroconvulsive shock (ECS)‐induced convulsion in rats (ED50= 28 mg/kg p.o.); however, neither ECS‐ nor pentylenetetrazol (PTZ)‐induced convulsions in mice were prevented by vinpocetine. The compound did not attenuate aggressive behavior in isolated mice. Vinpocetine decreased spontaneous loco‐motor activity (SLA) without affecting the rectal temperature in rats at doses greater than 25 mg/kg p.o., but the decrease was not dose‐related. Neither 10 nor 50 mg/kg p.o. of vinpocetine antagonized amphetamine‐induced stereotypy and exophthalmos in rats. In mice, vinpocetine (up to 100 mg/kg p.o.) did not antagonize reserpine‐induced catalepsy and ptosis or protect against tremorine‐induced lacrimation, tremor, salivation, or hypothermia. The lack of effect in these tests demonstrates that vinpocetine has little, if any, propensity to produce central nervous system (CN

ISSN:0272-4391    

DOI:10.1002/ddr.430110205

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

年代:1987

数据来源: WILEY

摘要:

AbstractIn order to determine the role of the cholinergic system in the bronchoconstriction induced by hypotonic solutions 30 subjects were studied: 15 asthmatic patients and 15 healthy volunteers to whom distilled water was administered by inhalation through ultrasonic nebulization. All asthmatic patients showed a 20% reduction of forced expiratory volume in 1 sec in relation to the initial value. Bronchospasm was not detected in any of the healthy subjects. After 24 hr, ipratropium bromide in aerosol was administered 1 hr before distilled water nebulization, and this prevented the bronchoconstriction response in 11 of the 15 asthmatic patients. These results suggest that such bronchospasm is mediated at least in part by vagal reflex.

ISSN:0272-4391    

DOI:10.1002/ddr.430110206

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

年代:1987

数据来源: WILEY

摘要:

AbstractThe effect of toluene inhalation was studied on an operant behavior maintained by a fixed‐ratio (FR‐24) schedule of liquid reinforcement in rats. A dynamic (flow‐through) inhalational behavioral chamber was used to expose rats to toluene vapor. Rats were exposed successively to three graded concentrations (105, 214, 382 ppm) of toluene vapor each for 2 hr in range‐finding experiments during 6 1/4‐hr sessions. The reinforcement rate was not altered at hours 1 and 2 but was decreased at hours 3 and 5 of exposure. However, at hours 4 and 6 the reinforcement rate showed recovery from depression. In 2‐hr exposure experiments with four different concentrations of toluene on separate days, the reinforcement rate was decreased at hour 1 during exposure to 142, 211, and 496 ppm, but exposure to 121 ppm had no effect. There was also no effect when rats were exposed to 115 ppm of toluene during a 5‐hr session. The experiment with 2‐hr daily exposures to 212 ppm of toluene for 5 consecutive days indicated the development of tolerance to the decreased reinforcement rate during 4th and 5th days of exposure. This study thus shows a minimum effective concentration of 142 ppm of toluene, which would produce no effect on FR liquid‐reinforced behavior, and indicates that tolerance develops to the behavioral

ISSN:0272-4391    

DOI:10.1002/ddr.430110207

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

年代:1987

数据来源: WILEY

摘要:

AbstractThe safety of tolrestat use in the diabetic patient was demonstrated by data from 14 double‐blind and open‐label studies conducted in 1,300 patients with diabetic neuropathy; the results were supported by data from earlier bioavailability, pharmacokinetic, and clinical pharmacology trials. There was a generally comparable frequency of complaints in the tolrestat dose groups and placebo groups. In a year‐long double‐blind study, the only complaint considered to by “possibly” drug‐related that occurred with a significantly greater incidence in patients treated with tolrestat than in those on placebo was dizziness. Laboratory test values recorded during the trials supported the positive safety findings of tolrestat. A review of blood urea nitrogen and serum creatinine values did not suggest any potential for tolrestat‐induced renal dysfunction. Infrequently, significant elevations in serum hepatic enzyme (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) levels occurred, accounting for 27 of 42 possibly drug‐related patient withdrawals following tolrestat administration. On review of these cases, it was concluded that tolrestat may cause hepatocellular damage with coincident elevations in AST and ALT in approximately 2% of patients. Importantly, the abnormalities were reversible after discontinuing the drug, commonly within 8–16 weeks. There was no evidence of a hypersensitivity syndrome in any patient in any study. These results support a favorable safety pr

ISSN:0272-4391    

DOI:10.1002/ddr.430110208

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

年代:1987

数据来源: WILEY

ISSN:0272-4391    

DOI:10.1002/ddr.430110201

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

年代:1987

数据来源: WILEY