PubMed Health⌕ Search

Biomedical subjects

B Lerer

Publications and source records attributed to B Lerer.

At least 145 records · Page 8Linked to original sources
PubMed1990

Core symptoms of posttraumatic stress disorder unimproved by alprazolam treatment.

The authors report a random-assignment, double-blind crossover trial comparing alprazolam and placebo in posttraumatic stress disorder (PTSD). Ten patients fulfilling DSM-III criteria for PTSD completed 5 weeks of treatment on each agent. Improvement in anxiety symptoms was significantly greater during alprazolam treatment but modest in extent. Symptoms specific to PTSD were not significantly altered. The impact of nonspecific symptomatic effects on the outcome of drug trials in PTSD is considered.

Adult↗
PubMed1989

Post-receptor-mediated increases in adenylate cyclase activity after chronic antidepressant treatment: relationship to receptor desensitization.

Administration to rats of chronic electroconvulsive shock (ECS) or chronic desipramine (DMI, 10 mg/kg daily i.p. for 3 weeks) did not affect either basal or forskolin-stimulated adenylate cyclase activity in membranes prepared from the caudate nucleus. In cerebellar membranes prepared from rats which had received chronic ECS, forskolin-stimulated activity was significantly increased compared to activity in sham- or single ECS treated rats. Forskolin-stimulated adenylate cyclase was increased in both hippocampal and cerebellar membranes from rats which received chronic DMI, compared to saline-treated animals. In cerebellar membranes, increases comparable to those with forskolin were also obtained with guanylyl-5'-imidodiphosphate (GppNHp) after both treatments, while with Mn2+ ions, either alone or in the additional presence of forskolin, the changes observed were similar to those previously reported in cortical membranes. A possible mechanism for these effects was investigated by studying antidepressant-induced and in vitro desensitization of the cyclic AMP response in slice preparations from the various brain areas. In slices from caudate nucleus, chronic DMI did not alter stimulation of cyclic AMP formation by either noradrenaline or forskolin, while in cerebellar slices the noradrenaline response was significantly reduced, and in hippocampal slices both responses were reduced (heterologous desensitization). In vitro incubation of cortical slices with noradrenaline also resulted in a reduction in the response to both agents. However, in membranes prepared from the desensitized cortical slices, there was no change in the degree of activation of adenylate cyclase by either NaF or forskolin. Thus, the increase in these activities, observed in certain brain areas after chronic antidepressant treatment may not necessarily be related to beta-adrenoceptor desensitization.

Adenylyl Cyclases↗
PubMed1989

Peripheral versus central manifestations in the toxic interaction of lithium and pilocarpine.

Administration of a cholinomimetic agent 24 hr after a single injection of lithium chloride results in a profoundly toxic interaction. The lethality of the interaction was completely blocked by prior administration of scopolamine, but was not reduced by the peripherally acting cholinergic antagonist methscopolamine. Examination of the relative time courses of central neurotoxic and peripheral cholinergic manifestations showed that the peripheral manifestations were transient and were not enhanced by lithium pretreatment. The profoundly toxic consequences of lithium-cholinomimetic interaction may thus occur in the absence of enhanced cholinergic function in the periphery.

Animals↗
PubMed1989

Uptake of 3H-spiperone by lymphocytes in schizophrenia.

Uptake of 3H-spiperone into lymphocytes obtained from control subjects (N = 22), chronic schizophrenics (N = 20), relatives with psychiatric disorder (N = 11) and unaffected relatives (N = 17) was studied. No differences were observed in spiperone uptake among any of the groups examined. Although previous investigations reported marked differences in 3H-spiperone uptake between schizophrenic and control subjects, we were unable to replicate their findings: the failure to replicate those of Bondy and colleagues may well be due to our inability to duplicate in our laboratory the exact biochemical methodology described by these investigators. Saturation curves could not be determined for most subjects. In addition, chronicity of illness and long-term exposure to neuroleptic medication among the schizophrenic subjects may partially account for the contradictory results reported by different investigators.

Adult↗
PubMed1989

Effects of chronic electroconvulsive shock on D1 and D2 dopamine receptor-mediated activity of adenylate cyclase in homogenates of striatum and limbic forebrain of rat.

Stimulation of adenylate cyclase by dopamine in homogenates of the striatum was unaltered in rats which had received either a single or a series of 10 electroconvulsive shock, compared to those which received sham treatment. In homogenates of the limbic forebrain, stimulation by both 100 microM dopamine and by 4 microM SKF 38393 was significantly increased after chronic electroconvulsive shock. The activity of D2 receptors, as measured by inhibition of forskolin-stimulated adenylate cyclase, in the presence of the D1 receptor antagonist SCH 23390, was unaltered by chronic electroconvulsive shock in either area of the brain. The selective effect of chronic electroconvulsive shock in increasing the activity of D1 receptors may account both for the increase, in dopamine-mediated behaviour, seen after chronic electroconvulsive shock and for the antiparkinsonian effects of this treatment.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Modulation of second messenger function in rat brain by in vivo alteration of receptor sensitivity: relevance to the mechanism of action of electroconvulsive therapy and antidepressants.

1. The second messengers cyclic AMP and inositol triphosphate are the intracellular mediators for a number of neurotransmitters for which receptors exist on brain neurons. 2. Up- or down-regulation of these receptors in general produce corresponding changes in the associated second messenger systems. 3. Chronic administration of antidepressants including electroconvulsive shock to rats produces a number of changes in cerebral receptors, notably down-regulation of beta-adrenergic and serotonin 5-HT2 receptors and up-regulation of alpha-1 adrenergic receptors. 4. The changes in receptor number induced by such antidepressant treatments are in general accompanied by corresponding changes in the associated second messenger reactions. 5. Antidepressant administration has also been shown to induce increased post-receptor mediated adenylate cyclase activity in cortical membranes, and similar effects have also been reported in striatum after chronic administration of neuroleptics. The relevance of these effects to the mechanism of action of the drugs is discussed.

Animals↗
PubMed1989

Distinct memory impairments following electroconvulsive therapy and imipramine.

Memory functioning was assessed in 26 unmedicated patients with major depressive disorder (DSM-III) who were then administered either bilateral electroconvulsive therapy (ECT) (N = 16) or imipramine 200 mg per day (N = 10). The subjects were retested following seven ECT administrations or 21 days of imipramine treatment respectively. The retrograde memory tasks included recall of public and autobiographic events. The anterograde memory tasks included an immediate memory task, a verbal paired-associates recall task, and a non-verbal figure reproduction task. Depression was significantly improved in the ECT-treated subjects but not in those administered imipramine. Both ECT- and imipramine-treated patients showed a deficit in recent anterograde memory relative to their pretreatment performance, but no deficit in immediate memory. ECT-treated patients also had a significant and well-characterized impairment in retrograde remote memory. By contrast, imipramine-treated patients did not show a retrograde memory impairment which could be explained by treatment. The results suggest qualitatively different memory deficits produced by ECT and imipramine.

Depressive Disorder↗
PubMed1989

Prescribing patterns of neuroactive drugs in 98 schizophrenic patients.

Ninety-eight schizophrenic outpatients receiving pharmacotherapy were surveyed on two census days, 18 months apart. From this study sample it was found that, as recently as 1987, 18% of the patients were prescribed three classes of neuroactive drugs--16% two antipsychotic drugs simultaneously. Of antipsychotics receivers, 44% were prescribed anticholinergics, 3% antidepressants, and 4% benzodiazepines. Between census days, a significant shift from use of oral antipsychotics to the depot form of administration occurred, while polypharmacy frequency remained unchanged. An analysis of the data will provide guidelines for rendering a more rational pharmacological treatment.

Adolescent↗
PubMed1988

Effects of lithium and desipramine administration on agonist-stimulated inositol phosphate accumulation in rat cerebral cortex.

The effects of acute lithium and chronic desipramine administration on the inositol phosphate responses of rat cerebral cortical slices to noradrenaline, carbachol and 5-hydroxytryptamine, were determined. Acute injection of lithium (4 meq/kg s.c. 24 hr before sacrifice) significantly increased the inositol-1-phosphate response to noradrenaline, while chronic administration of desipramine (10 mg/kg i.p. for 3 weeks) produced a smaller increase in this parameter. Chronic desipramine also decreased the serotonin responses in terms of all three inositol phosphates measured. No potentiative or additive interactions between the lithium and desipramine effects were observed.

Animals↗
PubMed1988

Chronic electroconvulsive shock and desimipramine reduce the degree of inhibition by 5-HT and carbachol of forskolin-stimulated adenylate cyclase in rat hippocampal membranes.

The degree of inhibition of forskolin-stimulated adenylate cyclase activity by 5-HT and by carbachol in hippocampal membranes was significantly reduced after administration of either chronic ECS (10 days) or desimipramine (10 mg/kg i.p. for 3 weeks). A single ECS had no effect on the 5-HT response and slightly augmented the carbachol response. These results parallel previous observations on the effects of ECS and antidepressants on behavioral responses to 5-HT1a agonists and on muscarinic receptor number, and indicate the possible involvement of these receptors in the mechanism of action of antidepressant drugs.

Adenylyl Cyclases↗
PubMed1988

A controlled trial of phenelzine in posttraumatic stress disorder.

Thirteen patients meeting DSM-III criteria for posttraumatic stress disorder participated in a random-assignment, double-blind crossover trial comparing phenelzine (45-75 mg/day) and placebo. Ten patients completed at least 4 weeks of each treatment phase. Clinical response to phenelzine did not differ from placebo, and overall improvement by the end of the study could not be attributed to the active drug. The findings are discussed in the light of preliminary reports suggesting that phenelzine may be an effective treatment for posttraumatic stress disorder.

Adult↗
PubMed1988

Lithium modulation of second messenger signal amplification in man: inhibition of phosphatidylinositol-specific phospholipase C and adenylate cyclase activity.

The activity of phosphatidylinositol-specific phospholipase C was significantly reduced in platelets obtained from 20 euthymic manic-depressive patients on therapeutic lithium doses (mean blood level 0.85 mEq/l) compared to an age- and sex-matched group of 36 control subjects. The activities of prostaglandin E1-, aluminum/NaF-, and forskolin-stimulated platelet adenylate cyclase activity were also measured in a similar group of 16 lithium-treated and 22 control subjects. A marked reduction in both postreceptor (aluminum/NaF and forskolin) and receptor-stimulated (prostaglandin E1) platelet adenylate cyclase activity was observed in the lithium-treated group (mean blood level 0.81 mEq/l). These findings support the hypothesis that lithium's therapeutic mode of action in manic-depressive psychosis is mediated by the combined down-regulation of both principal second messenger systems, inositol phosphates and cyclic adenosine monophosphate, by reducing the activity of phosphatidylinositol-specific phospholipase C and adenylate cyclase.

Adenylyl Cyclase Inhibitors↗
PubMed1988

Cyclic AMP second-messenger signal amplification in depression.

Beta-adrenergic-mediated cyclic AMP accumulation was reduced in lymphocytes obtained from depressed patients from that observed in an age- and sex-matched group of control subjects. Among the depressed patients, those not responding to treatment showed significantly lower pretreatment responses to isoproterenol compared with patients who exhibited significant clinical improvement during antidepressant treatment. Late-night (terminal) insomnia was significantly associated with the blunted response to beta-adrenergic stimulation. In depressed patients with the lowest isoproterenol response, the effect of forskolin (which acts distal to the receptor and directly stimulates the catalytic subunit) on cyclic AMP accumulation was also significantly decreased. This suggests that post-receptor modulations of signal amplification also play a role in the reduced response to beta-adrenergic stimulation in depression.

Adult↗
PubMed1988

Post-partum psychosis in adult GM2 gangliosidosis. A case report.

Adult hexosaminidase A deficiency is a form of GM2 gangliosidosis with autosomal recessive inheritance. Only 35 cases (mostly among Ashkenazic Jews) have been reported worldwide. Symptoms include, in a third of the cases, psychosis. A 27-year-old sufferer with no prior psychiatric history, developed a post-partum psychosis, with affective and hebephrenic components, 3 days following her first delivery. She responded to lithium within 10 days of initiating treatment; the full episode lasted 1 month. We conclude that lithium is the preferred treatment for psychosis in such adult patients, especially in light of possible long-term neurological deterioration caused by phenothiazines. Ashkenazic Jews with atypical neurological syndromes presenting with psychosis should be tested for hexosaminidase A deficiency.

Adult↗
PubMed1987

Isoelectric focusing of human platelet phospholipase C: evidence for multimolecular forms.

Polyacrylamide gel isoelectric focusing was employed to characterize phospholipase C activity in the supernatant fraction after disruption of human platelets. Three bands of enzyme activity were detected on focused gels: a major band of activity (B) and two additional bands (A,C) were consistently identified. The isoelectric points of the three bands were in the range of pH 7.5-8.0. Phospholipase C activity was assayed using both phosphatidylinositol and phosphatidylinositol-4-monophosphate. The prominent B band was active against both substrates and no evidence for substrate preference towards phosphoinositides was obtained. These data suggest that isozyme forms of cystolic phospholipase C are present in human platelet supernatant and suggest the possibility of functional and structural differentiation of the various forms of the enzyme.

Animals↗
PubMed1987

Posttraumatic stress disorder in Israeli combat veterans. Effect of phenelzine treatment.

Twenty-five Israeli combat veterans fulfilling DSM-III criteria for posttraumatic stress disorder (PTSD) participated in an open, prospective trial of phenelzine sulfate administration (median daily dose, 60 mg; range, 30 to 90 mg); three patients withdrew early due to side effects. Treatment was continued for at least four weeks in 22 cases and thereafter for as long as it was felt to be of benefit. Therapeutic efficacy was rated using a new PTSD scale, the Hamilton Depression Scale, and the Hamilton Anxiety Scale administered at four weekly intervals. Six patients completed four to eight weeks of phenelzine treatment; seven patients, nine to 13 weeks; and nine patients, 14 to 18 weeks. Comparison of mean prediscontinuation scores with pretreatment ratings showed, at best, only small (23% to 38%) differences (on the PTSD and Hamilton Anxiety scales) in the group treated for nine to 13 weeks. Two patients with a concurrent diagnosis of panic disorder and two with a concurrent diagnosis of dysthymic disorder were the most improved symptomatically but fell short of clinically significant remission. Although statistically significant improvement was observed on seven of the 12 items of the PTSD scale, sleep disturbance was the only symptom showing a clinically impressive change. These results only partially support previous positive reports of phenelzine treatment of PTSD.

Adult↗