摘要:

AbstractThe cholinomimetic agents, physostigmine, neostigmine, and arecoline, and the anticholinergic agents, atropine, scopolamine, and methscopolamine, have been used to explore an acetylcholine hypothesis of affect disorders and stress. Cholinomimetic drugs cause many of the same effects as do naturally occurring stressors. These include increases in negative affect, the induction of affective disorders, increases in stress neuroendocrines including ACThH, cortisol, beta‐endorphin, growth hormone, prolactin, epinephrine, and noprepinephrine, increases in blood pressure and pulse rate, and increases in analgesia. These parallel effects, combined with the effect of stress on central acetylcholine activity, suggest a stress‐acetylcholine link

ISSN:0272-4391    

DOI:10.1002/ddr.430040202

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

年代:1984

数据来源: WILEY

摘要:

AbstractFluvoxamine, a new serotonin‐reuptake inhibitor, and imipramine were compared under double‐blind conditions in 36 unipolar and bipolar depressed inpatients. Both drugs produced significant reductions in depressive symptomatology over a 4–6‐wk course of treatment, with the greater part of the improvement occurring in the first 2 wk. No statistically significant differences were obtained between the two drugs. Adverse reactions, particularly anticholinergic ones, were much less frequently observed in the fluvoxamine group. No clinically significant laboratory abnormalities were reported for either treatment; but minor ECG irregularities were seen under both treatments. The findings generally correspond to results obtained in previous comparative clinical

ISSN:0272-4391    

DOI:10.1002/ddr.430040203

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

年代:1984

数据来源: WILEY

摘要:

AbstractSuriclone, a nonbenzodiazepine drug, shown to be anxiolytic in animal pharmacology, was investigated within a single dose tolerance and efficacy study using quantitative pharmaco‐EEG. The investigation showed that suriclone is tolerable in single oral doses of up to 0.8 mg, the highest dose given in healthy volunteers. The minimum effective dose producing statistically significant CNS action was 0.3 mg. Suriclone produced significant dose‐ and time‐related CNS effects. The onset of these effects was later than that of diazepam and its duration of action was longer. Suriclone was classified by the HZI computer EEG drug data base as anxiolytic at high doses. Among a variety of anxiolytics, the CNS effect of suriclone was most similar to that of diazepam. The optimal anxiolytic effective single dose of suriclone was predicted to be 0

ISSN:0272-4391    

DOI:10.1002/ddr.430040204

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

年代:1984

数据来源: WILEY

摘要:

AbstractCGS 13945 and CGS 13934 are two nonthiol ACE inhibitors having novel chemical structures. CGS 13945 is a monoester derivative of the free dicarboxylic acid CGS 13934. Based on studies from in vitro inhibition of ACE and in vivo inhibition of angiotensin I pressor responses, CGS 13945 must be hydrolyzed to CGS 13934 to express its optimal biological activity. Studies with rats reveal that CGS 13945 and CGS 13934 are orally effective inhibitors of ACE. Both inhibitors have a longer duration of action and are somewhat less effective than captopril. After oral administration, the bioavailability of the monoester CGS 13945 is greater than that of the free dicarboxylic acid CGS 13934. In the dog, CGS 13934 (i.v.) effectively inhibits angiotensin I pressor responses, but the esterified compound (CGS 13945) has only weak activity. This difference is presumably due to limited hydrolytic capacity of endogenous plasma esterase(s) in this species. However, both CGS 13945 and CGS 13934 potentiate the vasodepressor responses to bradykinin without affecting angiotensin II pressor responses.

ISSN:0272-4391    

DOI:10.1002/ddr.430040205

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

年代:1984

数据来源: WILEY

摘要:

AbstractCGS 13945 (1‐(4‐(ethoxycarbonyl)‐2,4‐dimethyl‐2R,4R‐butyryl)‐2,3‐dihydro‐2S‐indole‐2‐carboxylic acid) and CGS 13934 (its dicarboxylic acid derivative) are nonthiol angiotensin‐converting enzyme (ACE) inhibitors which have antihypertensive properties. Acute administration of CGS 13945 lowers systolic pressure in spontaneously hypertensive rats (SHR) and sodium depletion enhances the blood pressure reduction; the acute antihypertensive effects of CGS 13934 are minimal. Acute administration of CGS 13945 or CGS 13934 also elevates plasma renin activity, especially in sodium‐depleted SHR. CGS 13945 reduces systolic blood pressure of SHR in a dose‐dependent manner following oral administration on each of 4 consecutive days, whereas the antihypertensive effect of CGS 13934 is not apparent until the third day of drug administration. After 3 consecutive daily doses, 30 mg/kg (PO) of CGS 13945, CGS 13934 or captopril produce equal antihypertensive effects. CGS 13945 also reduces systolic blood pressure of sodium‐depleted normotensive rats. Daily oral administration of CGS 13945 to either sodium‐replete or ‐deplete perinephritic hypertensive dogs does not appreciably affect mean arterial pressure. Results suggest that CGS 13945 must be endogenously de‐esterified to the free acid form for endowment of optimal biological activity to inhibit the ACE. While the rat is apparently capable of such hydrolysis, the dog's capacity for endogenous h

ISSN:0272-4391    

DOI:10.1002/ddr.430040206

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

年代:1984

数据来源: WILEY

摘要:

AbstractThe effects of parenteral administration of diazepam (3 mg/kg), DL‐C‐allylglycine (60–80 mg/kg), and ketamine (20 mg/kg) on kainic acid (KA)‐induced limbic seizures were investigated in cats. Single microinjections of KA (1–4 μg) into the amygdaloid complex were followed by local sustained paroxysmal discharges in the limbic system. Seizures consisted of tonic clonic EEG discharges accompanied by orienting reaction to the ipsilateral side of injection and masticatory movements, facial jerks, and aggressive behaviour. Ictal discharges occurred every 5–10 min during the first hours after KA injection and then progressively disappeared within 1 wk. Interictal discharges remained for longer periods, but after 3 or 4 wk they were abolished. Diazepam completely blocked limbic seizures but not high‐frequency discharges in the site of injection and the ipsilateral hippocampus. The animals were protected for 30 to 60 min. At the same time, diazepam decreased multiple‐unit activity in the pontine reticular formation and the lateral geniculate nucleus and produced a general hypotonia state. DL‐C‐allylglycine activated KA amygdaloid focus during the remission state and ketamine produced independent epileptiformlike activity which interfered with that prod

ISSN:0272-4391    

DOI:10.1002/ddr.430040207

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

年代:1984

数据来源: WILEY

摘要:

AbstractAlthough some in vitro studies have raised the possibility that endogenous purines mediate the therapeutic effects of the benzodiazepines, no behavioral studies have been performed to confirm or reject this hypothesis. Consequently, inosine and the adenosine A1 receptor agonists N6‐ (L‐phenylisopropyl) adenosine (L‐PIA) and 2‐chloroadenosine (2CA) were evaluated for diazepam‐like anxiolytic activity in the pentylenetrazol‐saline discrimination model of anxiety. Rats were trained to press one of two levers for food reward after pentylenetetrazol (PTZ) injection (20 mg/kg) and to press the other after saline injection. During testing in these rats, diazepam (10 mg/kg) blocked the PTZ‐induced selection of the PTZ‐appropriate lever (i.e., rats selected the saline‐correct lever). Inosine, L‐PIA, and 2CA neither blocked selection of the PTZ‐appropriate lever after PTZ administration nor did they reverse the diazepam blockade. It is suggested that adenosine or inosine may not act endogenously to mediate the anxiolytic effec

ISSN:0272-4391    

DOI:10.1002/ddr.430040208

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

年代:1984

数据来源: WILEY

摘要:

AbstractActive social interaction (SI) and aggression (AGG) were recorded separately during 5‐min observation periods of pairs of male Wistar rats. There was little difference between the levels of SI in undrugged animals across ten different experimental conditions, involving the manipulation of environmental and social stimuli. When animals were housed and tested together, no increases in SI were observed with acute administration of chlordiazepoxide (CDZP, 8 mg/kg PO) irrespective of other environmental changes. When the only potentially anxiogenic stimulus used was a novel partner, a large increase in SI was observed with CDZP. With the exception of strong lighting, combinations of this and other stimuli resulted in smaller increases. When animals were housed and familiarized together but tested with a novel partner, the large increase in SI induced by CDZP was not associated with changes in locomotor activity and was maintained after subacute dosing when decreases in motor activity were absent. Furthermore, similar increases were observed with other benzodiazepines after acute administration in this protocol. This modified method of SI in the rat is more sensitive to the anxiolytic activity of benzodiazepines leading to their detection after acute administratio

ISSN:0272-4391    

DOI:10.1002/ddr.430040209

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

年代:1984

数据来源: WILEY

摘要:

AbstractThe antinociceptive activity of clonidine was investigated in two models of pain using the modified Haffner tail clip test (MHA) in mice and the formalin test (FT) in rats. Morphine was used as a positive control for comparison. Clonidine at does from 0.5 mg/kg to 8 mg/kg SC was not effective in MHA while morphine administration resulted in a dose‐dependent increase in the latency to bite the clip and an ED50of 1.2 mg/kg SC. No antinociceptive activity was observed for clonidine using the FT up to a dose of 4 mg/kg SC which causes severe behavioral depression. The ED50for morphine in FT was 1.7 mg/kg SC. From these studies we conclude that clonidine is not active in all tests used to predict analgesic efficacy in man. Additional analgesic and centrally acting drugs were also included for comparative purposes. Of the compounds tested only the opiates active in FT and MHA and cholinesterase inhibitors (active in MHA only) showed analgesic effect

ISSN:0272-4391    

DOI:10.1002/ddr.430040210

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

年代:1984

数据来源: WILEY

摘要:

AbstractCastor oil‐induced diarrhea in rats is described to be an appropriate model of the complex, prolonged processes of hypersecretion and accelerated transit that characterize secretory diarrhea. Suprofen, a prostaglandin biosynthesis inhibitor, was found to postpone diarrhea over a wide dose range, but suprofen failed to reduce the diarrheal excretion. In contrast to suprofen, loperamide not only increased the diarrhea‐free period but also produced a dose‐related decrease of the diarrheal excr

ISSN:0272-4391    

DOI:10.1002/ddr.430040211

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

年代:1984

数据来源: WILEY