摘要:

Abstract:Cathinone is an alkaloid that has been discovered some fifteen years ago in the leaves of the khat bush. This plant grows in East Africa and in southern Arabia, and the inhabitants of these regions frequently chew khat because of its stimulating properties. Cathinone, which is S(–)‐α‐aminopropiophenone, was soon found to have a pharmacological profile closely resembling that of amphetamine; indeed, in a wide variety ofin vitroandin vivoexperiments it was demonstrated that cathinone shares the action of amphetamine on CNS as well as its sympathomimetic effects; thus, for example, drug‐conditioned animals will not distinguish between cathinone and amphetamine. These various observations were confirmed by a clinical experiment showing that cathinone also in humans produces amphetamine‐like objective and subjective effects. Finally, it was demonstrated that cathinone operates through the same mechanism as amphetamine, i.e. it acts by releasing catecholamines from presynaptic storage sites. Thus, much experimental evidence indicates that cathinone is the main psychoactive constituent of the khat leaf and that, in fact, this alkaloid is a natural a

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00434.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Studies of the behaviourally‐reinforcing actions of opioid and stimulant drugs of abuse are reviewed in an attempt to identify their reward‐related brain receptors. We focus on data generated by drug self‐administration, brain stimulation reinforcement, and conditioned place preference paradigms. A consistent body of evidence supports a role for μ and δ, but not K, receptors in opioid reward. Stimulant reward apparently involves both D1and D2receptors; the data favour D2mediation of stimulant drug reinforcement with a permissive or modulatory role for D1receptors. The reward‐relevant opioid and dopamine receptors, as well as the cannabinoid (marijuana) receptor, share the ability to couple Giproteins that mediate inhibition of adenylate cyclase and stimulation of K+conductance. These signal transduction mechanisms thus may be generally implicated in the reinforcing properties of diverse drugs

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00435.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00436.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:The second derivative of developed tension (T”, d2T/dt2) has not come into common use in the analysis of cardiac contractility, although it has been shown to give additional information on the myocardial contraction‐relaxation cycle (CRC). In the present study a new way to use T”in the analysis of myocardial mechanics, including the time course of T”, is described. Profiles of the T”of the some drugs with established cardiotonic effects are presented. Experiments were carried out in spontaneously beating whole rat atria preparations. The effects of changing contraction frequency on the measured parameters were studied with electrically paced left atria. Qualitative inotropic effects of 1‐methyl‐3‐isobutylxanthine (MIX), theophylline, caffeine, milrinone, isoprenaline and forskolin were studied. Concentrations equief‐fective with respect to the force of contraction were tested. Inotropic profiles were evaluated at the time of maximal force of contraction. We found that methylxanthines have a mechanical behaviour quite distinct from other inotropic agents acting via cAMP. The effects of MIX were similar to those of theophylline in all respects. A tendency to increase the active relaxation phase of T”was a property common to methylxanthines. Caffeine also prolonged the phases of contraction, whereas MIX and theophylline have opposite effects. Milrinone in turn mimics the effects of isoprenaline and forskolin; abbreviation of the relaxation phase of T”was the feature most typical of them. Caffeine was the only agent which did not shorten the duration of CRC. The method proved valuable in basic research on drug effects on

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00437.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:The acute effects of single oral doses, 0.4 and 2.0 mg/kg, of trichothecene T‐2 mycotoxin on behaviour, motor performance and nociception were studied in male Wistar rats. Both doses are sublethal and did not cause overt acute signs of intoxication. In the open field test, 2.0 mg/kg of T‐2 toxin increased motionlessness and decreased sniffing (P<0.05) 4 hr after the administration. The higher dose shortened step‐through latencies in the test trial of the 24‐hr passive avoidance test (two‐way shuttle box). The exponential data analysis showed that, in those rats that did not learn to avoid the dark (unsafe) compartment of the box, the retention after 2.0 mg/kg of T‐2 toxin was only 25% of that in controls (P<0.001). T‐2 toxin had no effect on motor coordination in the rotarod test and in the bridge walking test 7–8 hr after administration. T‐2 toxin had no effect on nociception in the hot place test 8.5 hr after administration. The results suggest that T‐2 toxin has some inactivating effects on behaviour of rats, and it seems to cause an impairment in the passive avoidance tes

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00438.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:A behavioural study of the domoic acid (DOM)‐induced convulsive behaviour after intracerebroventricular administration was carried out in rats and mice. DOM‐induced behaviours were compared to those elicited by other excitatory amino acid (EAA) agonists N‐methyl‐D‐aspartate (NMDA), α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) and kainic acid (KA), in such a way as to assess the possible similarities between DOM‐induced effects and EAA subtype receptor activationin vivo. In rat, DOM (0.03–3 nmol/rat) caused a complex pattern of convulsive behaviour, quantified by means of a 15‐point rating scale. DOM‐induced behavioural profile was characterized at the lower doses by “preconvulsive” behaviours as wet dog shakes, hypermotility, mild facial clonus. At higher doses, DOM caused clonic convulsions followed by the “status epilepticus” syndrome (wet dog shakes, forelimb clonus, rearing, salivation). Rats treated with KA (0.3–10 nmol/rat) showed an almost identical behavioural profile. AMPA (1–10 nmol/rat)‐induced convulsive behaviour was similar to DOM and KA only at the higher doses. NMDA (0.25–10 nmol/rat) caused clonic convulsions but not “status epilepticus”. In mice, similar results were obtained: all the tested drugs induced generalized seizures, but only animals treated with DOM, KA and AMPA showed a prolonged sequence of seizures with forelimb clonus. Our results confirm the findings reported in the literature and support the hyp

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00439.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Single‐dose intravenous injections of desipramine to rats resulted in a distribution pattern typical of basic lipophilic drugs, i.e., highest concentrations in lung and lowest in adipose tissue and plasma. In contrast, after N‐acetyldesipramine, a non‐basic analogue of desipramine with comparable lipophilicity, concentrations of this drug in adipose tissue were much higher than in lean tissue or plasma as a result of redistribution into the former and rapid disappearance from the latter tissue. N‐Acetyldesipramine had much lower plasma and tissue half‐lives than desipramine, but at the same time a much higher adipose/plasma concentration ratio and adipose storage index. Chronic administration of the basic lipophilic drug, haloperidol, to rats in their diet over 21 days resulted in a steady‐state distribution pattern with highest concentrations in lung and lowest concentrations without accumulation in adipose tissue. This study provides additional evidence for the influence of basic groups on the distribution of lipophilic drugs. Thus, basic lipophilic drugs do not undergo redistribution into adipose tissues, possibly because of a competition by stronger binding to lean tissue as a result of lyso

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00440.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Antinociception and central nervous system depression (CNSD) caused by intraperitoneal, intrathecal and subcutaneous administration of oxycodone or morphine were studied in a randomized and blind, saline controlled study in rats. Antinociception was assessed with the tail‐flick and hot plate tests. CNSD was assessed by testing the corneal, placing and righting reflexes and with a 4‐point catalepsy score. Intraperitoneally and subcutaneously administered oxycodone and morphine were given in doses of 2.5–10 and 5–20 mg kg–1respectively. The intrathecal doses were 12.5 μg and 100 μg of oxycodone and 6.25 μg and 50 μg of morphine. In both nociceptive tests subcutaneously and intraperitoneally administered oxycodone was 2–4 times more potent than morphine, while intrathecal morphine was over 14 times more potent. CNSD was more profound with oxycodone than with morphine after intraperitoneal and subcutaneous administration, but was not observed after intratechal administration of either drug. Differences in opioid receptor affinities, liposolubilities and metabolism are discussed as possib

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00441.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Rats were treated by intraperitoneal injection for four weeks with either RU24969, a 5‐HT1Band 5‐HT1Aagonist or imipramine, a 5‐HT uptake inhibitor. Pre‐ and postsynaptic 5‐HT receptors were measured to compare the effect of direct or indirect stimulation of the 5‐HT autoreceptor (5‐HT1Breceptor). The 5‐HT transport protein (5‐HT uptake site), labelled with [3H]paroxetine, was unaffected after treatment with either one of the drugs. The density of 5‐HT2 receptors, labelled with [3H]ketanserin, we found increased after treatment with RU24969 (Bmax=161 fmol/mg protein) and decreased after treatment with imipramine (Bmax=109 fmol/mg protein) as compared with control rats (Bmax=134 fmol/mg protein). The 5‐HT1Breceptor was found decreased both by the imipramine treatment (Bmax=106 fmol/mg protein) and the treatment with RU24969 (Bmax=105 fmol/mg protein), compared with control rats (Bmax=130 fmol/mg protein). The 5‐HT1Areceptor was found to be decreased after treatment with RU24969 (control: Bmax=62 fmol/mg protein; RU24969‐treated: 49 fmol/mg protein), but unchanged after treatment with imipramine (Bmax=58 fmol/mg protein). These results correspond to what could be expected, if the 5‐HT1Brecept

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00442.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:A randomised, placebo‐controlled, double blind single‐dose cross‐over study was arranged to investigate possible interactions between zopiclone (7.5 mg) and two widely used benzodiazepine (BZD) anxiolytics diazepam (5 mg) and lorazepam (1 mg) during the elimination phase of drugs. Psychomotor performance was tested before and 1, 6, 8, 12 and 24 hr after the drug administration. Simultaneously, blood samples were drawn for determination of plasma drug concentrations. The elimination of each compound was not altered by coadministration of other drugs. As expected, one hour after drug ingestion, psychomotor performance was impaired. The coadministration of drugs increased the effect. During the elimination phase, 6 and 8 hr after the drug intake, only zopiclone and lorazepam in combination slightly impaired performance as compared with the pretreatment levels, but there was no difference as compared with placebo. Adverse events after active treatments were not significantly different from those after placebo. At the recommended dose of 7.5 mg, zopiclone does not alter the elimination pharmacokinetics of the BZD anxiolytics diazepam (5 mg) and lorazepam (1 mg), and neither is the elimination of zopiclone affected by these BZDs. Due to the rapid elimination of zopiclone, the increase in sedation seen after concurrent administration with BZDs is of short dur

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb00443.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY