[Evolutionary aspects of bipolar disorder].
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Adolescent↗
Biomedical subjects
V Caillard
Publications and source records attributed to V Caillard.
Comparative effects of low and high doses of clomipramine and placebo in panic disorder: a double-blind controlled study. French University Antidepressant Group.
This study was designed to explore the dose-response relationship for clomipramine in patients with panic disorder, with or without agoraphobia. After 1 week of single-blind placebo pretreatment, 180 such patients were assigned to a multicentre placebo-controlled comparison of the effects of high and low doses of clomipramine, and were followed up for 8 weeks. In alleviating anxiety and panic disorder, both clomipramine doses were more efficacious than placebo for panic disorder and, to a lesser degree, for phobia. The lower dose was better tolerated and at least as effective as the higher dose, sometimes more so. These results indicate the clinically important possibility that low-dose clomipramine is effective and well tolerated.
Adolescent↗
The chemotherapy of rodent malaria. LIII. 'Fenozan B07' (Fenozan-50F), a difluorinated 3,3'-spirocyclopentane 1,2,4-trioxane: comparison with some compounds of the artemisinin series.
Fenozan B07, a difluorinated 3,3'-spirocyclopentane, 1,2,4-trioxane, is a novel, second-generation antimalarial endoperoxide which is a potent blood schizontocide against strains of rodent malaria that are highly resistant to a wide spectrum of classical antimalarials. Like compounds of the artemisinin series, its action is limited to the intra-erythrocytic stages, both asexual and sexual, and it is devoid of causal prophylactic activity. Both Fenozan B07 and the artemisinins are potent gametocytocides. In contrast to arteether, in a model using synchronous infection with Plasmodium vinckei petteri, Fenozan B07 inhibits the development of all asexual stages except preschizonts, as well as gametocytes. The activity of the artemisinin series in rodent-malaria models is limited to the rings and young trophozoites. The combined effect of Fenozan B07 with artesunate against P. v. petteri was only additive. A slight degree of potentiation was found in mice infected with asynchronous, drug-sensitive P. berghei but the combination was only additive against CQ-resistant P. yoelli ssp. NS. On the other hand, a significant degree of synergism was observed when mice infected with the artemisinin-resistant ART line of P. yoelii ssp. NS received combinations of Fenozan B07 with artemisinin. The conclusion is drawn from these and other data that there are significant differences between the blood schizontocidal actions of Fenozan B07 and the artemisinins. The basis of these differences remains to be determined.
Animals↗
Stage sensitivity of Plasmodium vinckei petteri to quinine, mefloquine, and pyrimethamine.
The stage-dependent sensitivity of Plasmodium vinckei petteri to the antimalarial drugs quinine, mefloquine, and pyrimethamine was investigated using single subcurative doses and 2 different tests: a prepatency test evidencing the extension of the prepatent period according to the stage at which the drug was administered, and a patency test showing the morphological alterations of the parasites and the modifications of the parasitic pattern following drug treatment. Quinine activity was maximal when it hit the midterm trophozoite. No pigment clumping was seen and parasites developed normally until they reached the schizogonic stage when they became morphologically altered and unproductive. Mefloquine also acted on the midterm trophozoites. Parasites at this stage were killed immediately by the drug as evidenced by their degenerative appearance, and dead parasites lingered in the blood smears for at least 6 hr. However, although mefloquine was active during at least 48 hr (2 cycles), some trophozoites escaped destruction. The schizont stage was found to be the most sensitive to pyrimethamine, as previously reported for other parasite species. These results add to our previous reports showing that each drug acts preferentially on a specific stage of parasite development.
Animals↗
Chronobiology and chronotherapy of malaria: investigations with murine malaria models.
The schizogonic rhythm of rodent malarias in the blood of mice varies from one species or subspecies to the other. Synchronous strains enable a precise study of the sensitive stage of the parasite to antimalarial drugs. Asynchronous strains are less sensitive than synchronous strains because of the delayed penetration of merozoites into red blood cells.
Animals↗
Plasmodium vinckei petteri: identification of the stages sensitive to arteether.
Antimalarial activity of arteether, a derivative of artemisinin (qinghaosu) against blood-induced infections of the highly synchronous Plasmodium vinckei petteri rodent species of malaria was evaluated in Swiss mice. A single subcurative dose of arteether of 2.2 mg/kg body weight was injected subcutaneously to mice, either during the prepatent period or during the patent infection, when different stages of the parasitic cycle were present in the blood. It was shown that rings and young trophozoites were the most susceptible stages to arteether. The drug had no effect on merozoites and little effect on mid-term trophozoites which is the stage most sensitive to chloroquine. The alcoholic solution (10% alcohol in sterile water) had an immediate effect while the oily solution (miglyol 840) was active between 3 and 21 hr after injection.
Animals↗
Sertraline in the prevention of depression.
A group of 480 patients, aged 19-78 with an HRSD score of at least 17 and who met DSM-III criteria for major depressive disorder were studied. Patients were given placebo for a one-week single-blind run-in period, after which sertraline was administered for eight weeks. This was followed by 44 weeks in which patients received sertraline or placebo on a double-blind, randomised basis. Patients were assessed periodically using the 17-item HRSD and the Clinical Global Impression scales. During the entire double-blind period 24 (13.0%) sertraline patients relapsed compared with 48 (45.7%) placebo patients (P less than 0.001). The protective effect of sertraline was maintained throughout the 44 weeks. The study provides evidence that sertraline prevents relapse of the index episode of depression as well as recurrence of further episodes and has few side-effects.
1-Naphthylamine↗
Chronotherapy of malaria: identification of drug-sensitive stage of parasite and timing of drug delivery for improved therapy.
The cyclic nature of malarial fever in conjunction with the pharmacokinetic characteristics of antimalarial drugs, call for the conception of a chrono-therapeutic approach for the treatment of the disease. An experimental murine malarial model was devised using the highly synchronous species Plasmodium vinckei petteri to test this rationale. Sub-curative doses of chloroquine were injected sub-cutaneously to mice either during the prepatent period or during patent infection. Inspection of the effect of drug applied at different stages of the parasitic cycle, revealed that medium size trophozoites (MT) were the most susceptible stage to chloroquine, while ring and young trophozoite stages were refractory to the drug. Chloroquine given during these latter stages, affected the parasites when they developed into the MT stage. Drug treatment during the MT stage phase-shifted the schizogonic cycle by 18 hours. Hence, treatment with two consecutive injections given 18 hours apart, i.e. timed to the overwhelming presence of the MT stage in the circulation, gave the best therapeutic results.
Animals↗
Compared efficacy of prazepam and clomipramine in major depression with anxiety: a multicenter controlled study.
UNLABELLED: The efficacy of antidepressants is well established in major depressions, especially those with melancholic features. However, some anxiolytics also appear to have antidepressant properties at least for outpatients. 118 outpatients (25 males, 93 females, age: 18-60) with major depression according to DSM-III criteria, neither melancholic nor suicidal, reaching at least 27 on Montgomery and Asberg depression rating scale (MADRS) and 19 on Hamilton anxiety rating scale (HARS) accepted to participate this double blind study carried out by 15 G.P.s coordinated by 3 psychiatrists. After a one week placebo wash-out-single-blind period, they were randomly, double blind, assigned to one of the two following groups: PR treated with prazepam (30-60 mg), a benzodiazepine anxiolytic or CL treated clomipramine, an imipramine antidepressant (75-150 mg). Patients were evaluated at days 0, 7, 14, and 28, using MADRS, HARS, Clinical Global Impression and Hopkins symptoms check list 58. In addition, G.P.s had to meet monthly for a case discussion group. RESULTS: groups were comparable at day 0. A highly significant improvement of MADRS and HARS scores (p less than 0.001) was observed in the total population. For the completer population evolution was also significantly positive in all the parameters studied but, considering MADRS and HSCL scores, a difference in favor of CL is observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Striatal D2 dopaminergic receptors assessed with positron emission tomography and [76Br]bromospiperone in untreated schizophrenic patients.
Striatal D2 dopaminergic receptors of 12 drug-free schizophrenic patients and 12 normal subjects were investigated with positron emission tomography and [76Br]bromospiperone. Patients were classified according to DSM-III criteria, and their clinical symptoms were rated according to Andreasen's negative and positive symptom scales. The ratio of striatal to cerebellar radioactivity was taken as an index of striatal D2 dopamine receptor density. There was no significant difference between the control subjects and the overall schizophrenic group and no significant relationship between this index and the symptom ratings. However, state-dependent variables could partly account for the striatal D2 receptor density variability.
Adult↗
Targets for neurotransmitter receptor research using PET scan: the neuroleptic binding site.
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Adult↗
Striatal dopamine receptor occupancy during and following withdrawal from neuroleptic treatment: correlative evaluation by positron emission tomography and plasma prolactin levels.
The percentage occupation of striatal dopamine D2 receptors has been evaluated in 25 patients using 76Br-bromospiperone positron emission tomography (PET) and prolactin plasma levels (PRL) during oral neuroleptic treatment (11 studies), 1-90 days following discontinuation of such treatment (16 studies), and 1-120 days after last intramuscular administration of depot neuroleptics (nine studies). The PET-estimated occupation was highly significantly correlated in a sigmoid-like fashion to the logarithm of the chlorpromazine-equivalent dose of oral neuroleptics (suggesting a strict dose-occupation relationship during oral neuroleptic treatment and supporting the D2-mediated hypothesis of neuroleptic action), while PRL was weakly related to daily dosage. Following withdrawal, return to normal receptor availability, as estimated by PET, occurred within 5-15 days (suggesting that protracted effects of neuroleptics after withdrawal are not due to sustained D2 receptor occupation), but PRL values fell even more rapidly. Efficient treatment with depot neuroleptics resulted in marked PET-estimated D2 receptor occupation, stable over the whole 4-week drug-administration interval, suggesting that longer intervals could be appropriate; PRL values bore no relationship to PET-estimated occupation, indicating variable intersubject tolerance to neuro-endocrine dopamine blockade. Overall, PET was much more sensitive than PRL to estimate striatal D2 receptor occupation in vivo.
Adult↗
Striatal D2 dopaminergic receptor status ascertained in vivo by positron emission tomography and 76Br-bromospiperone in untreated schizophrenics.
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Adult↗
Substantial rise in sparteine metabolic ratio during haloperidol treatment.
A sparteine test was carried out in 14 patients suffering from acute schizophrenic psychoses before and 1-2 times during oral haloperidol treatment in doses of 10-40 mg day-1. In patients classified as extensive metabolisers (sparteine MR less than 20 before treatment), haloperidol treatment resulted in a rise in sparteine MR that correlated with the serum-haloperidol concentration both within and between patients. At the highest serum haloperidol concentrations (60-80 nM) an increase in sparteine MR by a factor 15-50 was seen, but no patients were transformed into phenotypically poor metabolisers. The steady state concentration of haloperidol on the initial standard dose of 10 mg day-1 was the same in one patient classified as a sparteine poor metaboliser (MR = 112) as in eleven patients classified as extensive metabolisers (MR:0.22-1.47).
Adult↗
Sertraline: a new antidepressant.
The authors review preclinical data; clinical pharmacology data; and efficacy data of sertraline, a novel serotonin uptake inhibitor. Both in vitro and in vivo, sertraline is a potent and specific serotonin uptake inhibitor (possessing up to 10 times the activity of similar agents). Chronic dosing produces down-regulation of beta-adrenergic receptors. In man, sertraline inhibits platelet serotonin uptake and is devoid of obvious cardiac effects. The plasma half-life of sertraline is 25 hours. Studies on psychomotor performance show little or no effect at doses up to 100 mg, whereas 200 and 400 mg appear to possess some sedating action. Sertraline exhibits acute antidepressant effects in the dose range 50 to 200 mg/day; in addition, in the same dose range it prevents recurrence of depression. Its side-effect profile is similar to that of drugs of the same class (dry mouth, nausea, and diarrhea being the most prominent); it lacks the obvious anticholinergic and sedating effects of amitriptyline.
1-Naphthylamine↗
Treatment of mania using a calcium antagonist--preliminary trial.
A study was undertaken on the effects on pure manic syndromes of the reduction of intracytoplasmic ionized calcium by administration of a calcium antagonist. Four well-known bipolar patients (manic type) were significantly improved. 1 patient was rapidly cured, though in this case (first attack in a young man) the possibility of spontaneous remission could not be excluded. 2 patients showed no improvement, suffering from a secondary manic state related to the onset of cerebral atrophy. If confirmed, these results should orientate future research in primary manic syndromes and in the mode of action of lithium on calcium metabolism.
Adult↗
[Treatment of mania by a calcium inhibitor. Preliminary study].
The authors are studying the effects on pure manic syndromes of reduction of intracytoplasmic ionised calcium through administration of a calcic inhibitor. Three wellknown bipolar patients (manic type) were significantly improved. One patient was quickly cured, but in this case (first access in a young man) spontaneous remission cannot be excluded. One patient was not improved, and presented a secondary manic state, related to a beginning cerebrary involution. These results, if confirmed, would orient future research in primary manic syndromes and in mode of action of lithium on calcic metabolism.
Adult↗
Open clinical study of cis(Z)-clopenthixol.
The antipsychotic effect and tolerance of cis(Z)-clopenthixol were studied in 13 patients with acute exacerbation of chronic schizophrenia. Seven patients were with CGI registered as improved after 28 days of treatment while 2 did not complete test treatment and the remaining 4 patients were considered unchanged. Significant average reduction of the initial total BPRS-score were registered throughout, while with NOSIE-30 a significant score reduction was seen only at day 28. The frequency of single side effects fell progressively during the treatment period. Dosages were individual and ranged at day 28 from 30 to 350 mg.
Adult↗