摘要:

AbstractThis report begins by reviewing data showing that the effects of acute exposure to stressful situations can grow with the passage of time (time‐dependent sensitization; TDS) and then proceeds to suggest that the clinical syndromes of panic, delayed post‐traumatic stress disorder, and bulemia represent instances of stressor‐induced sensitization to subsequent stressors. Finally, it discusses data demonstrating that a host of pharmacological agents—including antidepressants, antipsychotics, and anxiolytics—also show TDS after a single or brief period of treatment and proposes that induction of this phenomenon is due to the foreign/stressful properties of drugs. The report concludes with the suggestion that the very widespread ability of drugs to trigger effects that then grow with the passage of time—independent of repeated treatment—can form the basis of a new and revolutionary approach to ph

ISSN:0272-4391    

DOI:10.1002/ddr.430140102

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

年代:1988

数据来源: WILEY

摘要:

AbstractThe lipid composition of human immunodeficiency virus (HIV) was investigated. Several strains of HIV were found to contain considerable amounts of lipid. The major lipid constituents were cholesterol and phospholipid with a molar ratio close to one. This lipid composition and membrane apparent microviscosity, as determined by diphenylhexatriene fluorescent polarization, indicate that the HIV envelope is an extremely rigid membrane. A previous in vitro study and two recent clinical reports have indicated that AL‐721®, a lipid mixture designed to alter membrane lipid composition and organization by extraction of membrane cholesterol, has anti‐HIV activity. We found that AL‐721® modifies the lipid composition of HIV, reducing the cholesterol content and the cholesterol to phospholipid molar ratio. Both DPH fluorescent probe and endogenous protein fluorescent studies suggest that AL‐721® alters HIV envelope organization and/or apparent microviscosity. Membrane perturbation of HIV by AL‐721® may represent a new approach to

ISSN:0272-4391    

DOI:10.1002/ddr.430140103

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

年代:1988

数据来源: WILEY

摘要:

AbstractThe present study examined effects of the stereoisomers of celiprolol and further examined cardiostimulatory effects of celiprolol. In the anesthetized, ganglionicblocked dog, both I‐ and d‐celiprolol, 3 mg/kg, i.v., showed cardioselective beta adrenoceptor antagonist activity, although blockade of isoproterenol‐induced increases in heart rate and contractile force with I‐celiprolol was more effective. The two stereoisomers had equivalent cardiostimulatory effects, increasing heart rate by 24 ± 7 and 18 ± 3 beats/min and right ventricular contractile force by 37 ± 11 and 24 ± 11%, respectively (allP<0.05). After propanolol, 1 mg/kg + 0.3 mg/kg/hr, the cardiostimulatory effect of d‐celiprolol was abolished, whereas that of i‐celiprolol was unchanged. Dose‐response curves for heart rate and contractile force stimulation by d‐ and I‐celiprolol were parallel with I‐celiprolol being approximately 100 times more potent than d‐celiprolol and 3 times more potent than racemic celiprolol. These observations suggested that the physiologic effects of celiprolol may be largely mediated via I‐stereoisomer. In additional experiments cardiostimulatory effects of racemic celiprolol, 30 μg/kg, were inhibited by propranolol. Dose‐response curves for celiprolol alone and in the presence of propranolol were parallel. Beta‐blockade shifted the effects 1.5 log units to the right and affected chronotropic and inotropic activities similarly. Biochemical studies of celiprolol showed no significant inhibition of canine kidney sodium potassium ATPase, or of multiple forms of canine cardiac cyclic nucleotide phosphodiesterase. In conclusion, both I‐ and d‐celiprolol are cardioselective beta‐blocking agents with I‐celiprolol being the more potent stereoisomer. Also, the propranolol insensitive cardiac stimulatory activity of celiprolol may illustrate a complex interaction between beta antagonist with and withous ISA rather t

ISSN:0272-4391    

DOI:10.1002/ddr.430140104

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

年代:1988

数据来源: WILEY

摘要:

AbstractThree commonly used anesthetic agents (pentobarbital, chloralose‐urethane, and inactin) were studied in a rat model. The radiolabeled microsphere technique was used to evaluate rats anesthetized (no reaction to pain stimulus) with the three drugs as compared to awake unanesthetized animals. Of the three anesthetic agents studied, pentobarbital caused the smallest alteration in central hemodynamic parameters. Chloralose‐urethane significantly lowered cardiac output (56%), stroke volume (35%), and minute work (51%). Chloralose‐urethane also significantly increased total peripheral resistance (59%). Inactin at the concentration used in the present study had very little effect on cardiac index, heart rate, stroke volume, and minute work but significantly increased total peripheral resistance and mean arterial pressure. All three anesthetic agents reduced cerebral and skeletal muscle blood flows equally. While pentobarbital and chloralose‐urethane significantly decreased renal blood flow (33%), inactin did not change flow to the kidney. It is concluded that anesthetic agents used in small animal experiments should be chosen carefully so that they do not influence blood flow to the organ being

ISSN:0272-4391    

DOI:10.1002/ddr.430140105

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

年代:1988

数据来源: WILEY

摘要:

AbstractIntraperitoneal injection of scopolamine at a dose of 0.5 mg/kg produced a marked decrease after 15 min in the acetylcholine (ACh) content of the frontal and temporal cortices and the hippocampus in the rat. In the parietal and occipital cortices and the striatum, the decrease in ACh content was less extensive. When rats were treated with cholecystokinin octapeptide 15 min before the scopolamine administration, the decrease in ACh was prevented in a dose‐dependent manner. The choline content was not affected significantly by these treatment

ISSN:0272-4391    

DOI:10.1002/ddr.430140106

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

年代:1988

数据来源: WILEY

摘要:

AbstractThe autonomic effects of clovoxamine, a possible new antidepressant, were compared with placebo, imipramine, and amitriptyline in a double‐blind, repeated‐measures, latin‐square study design, using 16 healthy volunteers. Salivary flow, pupillary response, near‐point accommodation, and pilocarpine‐evoked miosis were assessed before and 1, 2, and 3 hours after each treatment condition. Dose‐related autonomic effects were seen with all three active drugs. Clovoxamine at a 50‐mg dose was not distinguishable from placebo. For salivary flow, perhaps the most reliable index of anticholinergic activity, the effects of 100‐mg and 150‐mg doses of clovoxamine were comparable to those of 50‐mg and 75‐mg doses of imipramine but were less than those of 50‐ and 75‐mg doses of amitriptyl

ISSN:0272-4391    

DOI:10.1002/ddr.430140107

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

年代:1988

数据来源: WILEY

摘要:

AbstractBaclofen was compared with diazepam for ability to block the interoceptive discriminative stimulus produced by the anxiogenic drug pentylenetetrazol (PTZ). Male hooded rats of the Long Evans strain were trained in two‐lever operant chambers to respond for food reward. Presses on one lever were reinforced after intraperitoneal injections of PTZ (20 mg/kg), and on the other lever after saline. After rats had acquired the PTZ discrimination, it was shown that pretreatment with baclofen failed to block the interoceptive stimulus produced by PTZ, whereas pretreatment with diazepam was effective. As baclofen is ineffective in a conflict procedure as well as in antagonizing the PTZ stimulus, but produces a diazepamlike interoceptive discriminative stimulus, it is concluded that elicitation of the diazepam stimulus may not be related to diazepam's anxiolytic efficacy and that diazepam discrimination may be an inappropriate model for studying anxiolytic properties of drugs. Furthermore, the difference between baclofen and diazepam with respect to anxiolytic efficacy is suggested to be related to receptor specificity. The binding of diazepam facilitates GABAAreceptor activity, whereas the binding of baclofen facilitates BABABreceptors Hence, it is suggested that modulation of GABAAreceptors may be critical in diazepam's blockade of the PTZ stimulu

ISSN:0272-4391    

DOI:10.1002/ddr.430140108

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

年代:1988

数据来源: WILEY

摘要:

Abstract1,2,3,4‐tetrahydro‐5‐amino acridine (THA), a cholinesterase inhibitor currently under investigation for use in the treatment of senile dementia, exhibited mutagenic activity with and without metabolic microsomal S‐9 activation against tester strain TA97a in theSalmonella typhimuriumincorporation assay. The mutagenic response was concentration‐dependent within the dose range of 500 to 2,500

ISSN:0272-4391    

DOI:10.1002/ddr.430140109

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

年代:1988

数据来源: WILEY

ISSN:0272-4391    

DOI:10.1002/ddr.430140101

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

年代:1988

数据来源: WILEY