ISSN:0272-4391    

DOI:10.1002/ddr.430010102

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

年代:1981

数据来源: WILEY

摘要:

AbstractBupropion is a novel antidepressant agent. In the present study, an attempt was made to gain some insight into the mechanism of the drug's antidepressant activity. In vitro studies revealed that bupropion was a weak, competitive inhibitor of norepinephrine (NE) uptake into rat hypothalamic synaptosomes and of dopamine (DM) uptake into rat striatal synaptosomes, having IC50 values of 6.5 ± 0.6 × 10−6M and 3.4 ± 0.4 × 10−6M, respectively. At 1 × 10−5M, the drug produced a 20 ± 3% inhibition of serotonin (5‐HT) uptake into rat hypothalamic synaptosomes. The drug was also a weak inhibitor of the ATP‐Mg+2stimulated uptake of NE and DM into synaptic vesicles of whole rat brain, having IC50 values of 3.3 × 10−5M and 6.0 × 10−5M, respectively. Bupropion had no dose‐dependent effect on the spontaneous release of NE, DM, and 5‐HT from these synaptosomal preparations in concentrations as high as 1 × 10−4M. Brain monoamine oxidase (MAO) activity in vitro was not affected by concentrations of the drug ranging from 10−7M to 10−5M. Bupropion was also without effect on brain MAO, 1 hr after i.p. doses in rats as high as 100 mg/kg. The ED50 value for bupropion necessary to inhibit the uptake of3H‐catecholamines by 50% into synaptosomes incubated in the serum from rats treated with the drug was 40 mg/kg i.p., while its ED50 value for antidepressant activity, as judged by the ability of bupropion to reverse the immobile posture of “helpless” rats, was 8 mg/kg i.p. These neurochemical properties of bupropion on uptake of biogenic amines and on MAO activity serve to distinguish it from other antidepressant drugs of t

ISSN:0272-4391    

DOI:10.1002/ddr.430010103

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

年代:1981

数据来源: WILEY

摘要:

AbstractClonidine, lidamidine, and loperamide each inhibited castor oil‐induced diarrhea in the rat. Clonidine and lidamidine, but not loperamide, also induced diuresis but at doeses above those producing antidiarrheal activity. Clonidine and lidamidine, but not loperamide, produced autonomic and central effects including piloerection, hypotonia, exopthalmus and ataxia at doeses similar to those producing antidiarrheal activity. These data suggest that only loperamide possesses selective antidiarrheal activit

ISSN:0272-4391    

DOI:10.1002/ddr.430010104

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

年代:1981

数据来源: WILEY

摘要:

AbstractSanguinarine, an isoquinoline alkaloid belonging to the benzophenanthridine class, has been found to be a time‐dependent inhibitor of cardiac Na,K‐ATPase activity. Enzyme inhibition depended on the concentration of enzyme in the assay. Dilution and centrifugation of the enzyme following incubation with sangunarine did not decrease inhibiton. Inhibiton of ouabain binding by sanguinarine was also time‐dependent and resulted in a reduction of the equilibrium level of ouabian bound to the enzyme preparation. This suggests the possibility that the positive inotropic effect of sanguinarine on the heart may be due to interaction with the cardiac glycoside receptor site on Na,K‐ATPase. Alternatively, sanguinarine may bind nonspecifically to phospholipids associated with the enzyme and exert its effects via conformational

ISSN:0272-4391    

DOI:10.1002/ddr.430010105

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

年代:1981

数据来源: WILEY

摘要:

AbstractIn 12 healthy male volunteers we studied the effect of nomifensine, an inhibitor of endogenous catecholamine reuptake, on insulin‐induced prolactin and growth hormone (GH) secretion. The effect of the drug on TRH‐induced prolactin secretion was also studied. Nomifansine was able to suppress completely the insulin‐stimulated prolaction secretion, whereas no effect on GH secretion was observed. TRH‐induced prolactin secretion was uninfluenced by t

ISSN:0272-4391    

DOI:10.1002/ddr.430010106

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

年代:1981

数据来源: WILEY

摘要:

AbstractThe inhibitory effect of topically applied flurbiprofen, a newer nonsteroidal antiinflammatory agent, on prostaglandin biosynthesis in human skin biopsies in primary irritant dermatitis was examined. The flurbiprofen‐treated areas synthesized significantly less PGE1(279 pg/mg dry weight) than placebo‐treated inflamed skin (626 pg/mg dry weight). The average inhibition in 11 treated patients was 55% (P<0.01 with Wilcoxon's signed rank test). Furthermore the anti‐inflammatory effect of flurbiprofen was clinically evaluated, and a poor correlation was found between the reduction of prostaglandin synthesis and the clinical effects of flurbip

ISSN:0272-4391    

DOI:10.1002/ddr.430010107

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

年代:1981

数据来源: WILEY

摘要:

AbstractThe influence of 49 compounds, among them 12 analgesics, on “wet dog” shaking (WDS) induced by thyroliberin (TRH) in rats has been investigated. WDS was dose dependently reduced by all of the analgesics and by 20 of the other drugs. The following compounds were the most active (ED50 values in parentheses): clonidine (5.4 μg/kg), fentanyl (9.6 μg/kg), oxotremorine (21 μg/kg), apomorphine (0.25 mg/kg), amphetamine (0.30 mg/kg), tetrabenazine (0.38 mg/kg), morphine (0.78 mg/kg), chlorpromazine (1.0 mg/kg), and ergotamine (1.2 mg/kg). Both agonists and antagonists of noradrenergic, dopaminergic, serotonergic, and GABA‐ergic functions were inhibitors of WDS, and antinociceptive activity was shared by most of the effective drugs.Thus, WDS or head‐shaking induced by TRH must be considered to be an expression of headache rather than such other causes as heat gain mechanisms or tremor induction. Prevention of TRH‐induced WDS may be used as a test of analge

ISSN:0272-4391    

DOI:10.1002/ddr.430010108

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

年代:1981

数据来源: WILEY

摘要:

AbstractAdult male hooded rats responding on three contact sensors for food reinforcement were trained to acquire a different three‐response sequence each day. Twelve three‐response sequences were used; with minor exceptions, the series of 12 was run four times in two rats and twice in one rat. Elapsed time and error rate for a given sequence declined over sessions and within sessions. Some sequences generated higher error rates than others. Results were generally consistent with previous results from pigeons emitting four‐response sequences. Application to the testing of drugs for therapeutic effects on cognitive deficits associated with aging is disc

ISSN:0272-4391    

DOI:10.1002/ddr.430010109

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

年代:1981

数据来源: WILEY

摘要:

AbstractRU 31124, a new anticonvulsant 1,4‐benzodiazepine was compared with clonazepam in a series of tests in rats and mice. It demonstrated greater anticonvulsant potency whilst having equivalent sedative properties to clonazepam. This profile of activity was confirmed in the photosensitive baboon,Papio papio, in which RU 31124 provided long‐lasting protection against convulsions at doses having little or no sedative side effe

ISSN:0272-4391    

DOI:10.1002/ddr.430010110

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

年代:1981

数据来源: WILEY

摘要:

AbstractAlfentanil, N‐{1‐[2‐(4‐ethyl‐4,5‐dihydro‐5‐oxo‐1H‐tetrazol‐l‐yl)ethyl]‐4‐(methoxymethyl)‐4‐piperidinyl}‐N‐phenyl propanamide monohydrochloride monohydrate, is a chemically novel, potent, extremely short‐acting and safe intravenous morphine‐like agent in laboratory animals. As an analgesic in rats, alfentanil is 137 times as potent as pethidine (tail withdrawal reaction test: i.v. ED50 is 6.04 mg/kg for pethidine and 0.044 mg/kg for alfentanil). The safety margin in rats is 1,080 (LD50: 47.5 mg/kg i.v.). Alfentanil reaches its peak effect within 2 min after injection, and its duration of action is very short: at two times its lowest ED50 the drug has a duration of action of 10 min. This duration is 30–35 min for pethidine and fentanyl, and 120 min for morphine. The narcotic antagonist naloxone produces an immediate and complete reversal of all morphine‐like effects of alfentanil. In dogs, alfentanil is a potent antiemetic (ED50: 0.032 mg/kg i.v.) with a safe

ISSN:0272-4391    

DOI:10.1002/ddr.430010111

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

年代:1981

数据来源: WILEY