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O Varoquaux

Publications and source records attributed to O Varoquaux.

At least 19 recordsLinked to original sources
PubMed2001

Clinical and neurochemical effect of acute tryptophan depletion in unaffected relatives of patients with bipolar affective disorder.

BACKGROUND: The lowering of mood induced by an acute tryptophan depletion (ATD) has been proposed as a candidate endophenotype for the vulnerability to manic-depressive illness. This study tests this hypothesis in relatives of probands from well-characterized multiplex families affected with bipolar affective disorder (BAD). METHODS: In a double-blind, crossover design, 20 unaffected relatives (URs) and 19 control subjects received either a 100-g amino acid (AA) drink devoid of tryptophan or a placebo, respectively. Clinical and biochemical effects of ATD were compared between unaffected relatives of BAD probands and age- and sex-matched control subjects. RESULTS: At 5 hours after AA drink ingestion, relative to the placebo, ATD resulted in 74% and 84% decreases in total plasma tryptophan concentrations in control subjects and relatives of patients with BAD, respectively. Unlike control subjects unaffected relatives experienced a lowering of mood during ATD but not with the placebo. Furthermore, URs tended to show increased impulsivity in the ATD condition. Measurements obtained before ingestion of the AA drink indicated that, relative to control subjects URs exhibited lower serotonin platelet concentrations, lower affinity, and fewer binding sites of the serotonin transporter for imipramine; these differences were unaffected by ATD. CONCLUSION: These results replicate and extend previous findings suggesting that URs of patients with BAD are more susceptible to low tryptophan availability. This finding may bear significance in the purported role of serotonergic mechanisms in the vulnerability to depressive syndrome and/or illness.

Acute Disease↗
PubMed1999

Decreased serotonin transporter binding in unaffected relatives of manic depressive patients.

BACKGROUND: There are numerous reports of decreased binding to platelet serotonin transporter (5-HTT) in depression, suggesting that it might be considered a trait marker of depression. To further investigate whether reduced 5-HTT function could be an endophenotype in manic depressive illness, we looked for abnormalities of platelet 5-HTT among subjects who are potential carriers of genetic vulnerability to manic depressive illness (MDI). METHODS: Blood samples were obtained from 20 unaffected relatives from families with at least two individuals with bipolar disorder and from 19 control participants. Plasma 5-HIAA, platelet 5-HT, and [3H] imipramine binding were measured. RESULTS: Unaffected relatives manifested lower platelet 5-HTT function than control participants as revealed both by reduced number and diminished affinity of imipramine binding sites and diminished platelet 5-HT content. CONCLUSIONS: These preliminary results suggest that reduced 5-HTT function could be considered a trait marker or an endophenotype in MDI.

Adrenergic Uptake Inhibitors↗
PubMed1995

Evaluation of the alpha 2-adrenoceptor blocking properties of buspirone and ipsapirone in healthy subjects. Relationship with the plasma concentration of the common metabolite 1-(2-pyrimidinyl)-piperazine.

1. Because the 5-HT1A agonist anxiolytic azapirones have a common alpha 2-adrenoceptor antagonist metabolite, 1-(2-pyrimidinyl)-piperazine (1PP), we measured central and peripheral alpha 2-adrenoceptor dependent responses before and after intravenous administration of 0.15 mg clonidine when healthy subjects were taking buspirone (30 mg day-1 for 4 days and 10 mg on day 5), ipsapirone (15 mg day-1 for 4 days and 5 mg on day 5) or placebo. 2. Clonidine decreased blood pressure, heart rate, oral body temperature, salivary excretion, plasma noradrenaline, 3,4-dihydroxyphenylglycol (DHPG) concentrations, increased plasma growth hormone but did not modify plasma insulin and C-peptide concentrations. Treatments tended to modify only the effect of clonidine on growth hormone (P = 0.07). 3. The azapirones reduced clonidine induced prolongation of choice reaction time (P = 0.015) and tended to antagonise clonidine induced fall in critical flicker fusion frequency (P = 0.066). 4. Only buspirone reduced total reaction time and increased critical flicker fusion threshold measured 12 h after the evening dose and these effects were correlated with the residual plasma 1PP concentration which was higher on buspirone than on ipsapirone (2.76 micrograms l-1, 95% CI:1.3-4.22 vs 0.65 microgram l-1, 95% CI: 0.32-0.98, P = 0.006). 5. Mean AUC of the 1PP plasma concentrations after the last dose of treatments were 3.7 times greater with buspirone than with ipsapirone (P = 0.0011). The AUC ipsapirone/AUC 1PP ratio was 6.45 and the AUC buspirone/AUC 1PP ratio was 0.076.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1994

A comparison of plasma homovanillic acid in the deficit and nondeficit subtypes of schizophrenia.

Plasma homovanillic acid (pHVA) was measured over a 13 hr-period in 16 DMS-III-R schizophrenic patients, all treated with neuroleptic drugs and in a stable clinical and therapeutic status for the preceeding 12 months. Patients were categorized into deficit (n = 9) and nondeficit (n = 7) forms of schizophrenia according to the Schedule for the Deficit Syndrome (SDS) criteria. As compared to the nondeficit group, deficit patients display significantly lower mean pHVA concentrations from 9 AM to 12 AM and a lack of diurnal variations. None of the demographic, clinical, and therapeutic variables can explain these biological differences. These data suggest a specific biochemical basis for the deficit syndrome of schizophrenia as defined by the SDS criteria, that is, primary, enduring, negative symptoms.

Adult↗
PubMed1993

Effect of molsidomine and linsidomine on the human isolated bronchus and the guinea-pig isolated trachea.

The effects of molsidomine and its metabolite linsidomine were studied on the guinea-pig isolated trachea and on the human isolated bronchus. These effects were compared with those of nitrate derivatives (sodium nitroprusside, isosorbide dinitrate), theophylline, zardaverine and isoprenaline. Linsidomine exerted a relaxant effect similar to that of sodium nitroprusside on the two types of preparations precontracted with acetylcholine, histamine or potassium chloride. Molsidomine was about one-hundredth as potent as linsidomine, and less efficacious. The effects of the two substances were not modified by removal of the human bronchial epithelium. The concentration-response curves of linsidomine and sodium nitroprusside were significantly shifted to the right by methylene blue (3 x 10(-5) M) but the effects of isoprenaline were unmodified. The effects of linsidomine and sodium nitroprusside were potentiated specifically by zaprinast (10(-6)-10(-5) M), an inhibitor of type Ia or V phosphodiesterases, whereas the effects of isoprenaline were potentiated by zardaverine (10(-9)-10(-8) M), an inhibitor of class III and IV phosphodiesterases. The effects of all three substances (linsidomine, isoprenaline and sodium nitroprusside) were potentiated equally by theophylline (10(-5)-10(-4) M), a nonspecific inhibitor of phosphodiesterases. It is concluded that linsidomine is a potent relaxant of the smooth muscle of the guinea-pig isolated trachea and human isolated bronchus. In terms of potency and efficacy, its effect is much superior to that of the parent compound molsidomine. It is suggested that linsidomine acts, like nitrate derivatives, through the guanylate cyclase-cGMP system.

Animals↗
PubMed1992

Compared plasma and brain pharmacokinetics of clomipramine and its metabolite demethylclomipramine in two strains of mice (NMRI and CD1).

The fate of clomipramine (CMI) and its main demethylated metabolite demethylclomipramine (DCMI) was studied in two strains of Swiss mice (NMRI and CD1) after intraperitoneal injection. A study of its distribution among various tissues showed that fixation was most marked in lungs, perirenal fat and kidneys, and only moderate in the brain. The pharmacokinetic parameters of both molecules were determined in brain tissue and plasma. Absorption was rapid (tmax CMI = 14 min), metabolism prompt (tmax DCMI = 17 or 18 min according to the breed) and elimination rapid from both plasma and brain tissue. The first two stages were similar in the two strains, but elimination of CMI from both plasma and brain was faster in the NMRI mice (plasma t1/2 = 53 min against 165 min in the CD1 mice). Both values were well below that reported for man (mean plasma t1/2 = 24 h). The data presented can serve as a basis for designing true chronic administration protocol in animals.

Animals↗
PubMed1990

Quinidine oxidative metabolism. Identification and biosynthesis of quinidine 10,11-dihydrodiol stereoisomers.

The isocratic reversed phase high performance liquid chromatographic method proposed for quinidine metabolic studies facilitates particularly the separation of 10(R) and (S) isomers of quinidine 10,11-dihydrodiols. The finding of each of these forms following a new synthetic pathway allows us to identify and quantify them in biological fluids. These two isomers have especially been observed in rat bile and hepatocyte secretions. The metabolic inducing effect of phenobarbital on the oxidative metabolism of quinidine is verified in rat isolated hepatocytes. Simultaneous secretion of the two dihydrodiols is also verified in human urine by a gas chromatography/mass spectrometry procedure.

Animals↗
PubMed1988

Pharmacokinetic patterns of repeated administration of antidepressants in animals. I. Implications for antinociceptive action of clomipramine in mice.

The pattern of repeated administration of antidepressants in animals varies from one study to another, making comparison of results difficult. We propose a means of standardizing the pattern of administration for any particular animal, based on a pharmacokinetic study of the antidepressant [here clomipramine (CMI)] in that animal. The plasma half-life (127 min) in the Swiss CD1 mouse was used as a basis for chronic administration, which was strictly every half-life as in clinical use. Daily administration is thus merely repeated acute administration. The antinociceptive action of CMI was compared under four sets of conditions of injection: single, chronic, daily and closely repeated (every 40 min). The antinociceptive effect obtained after an acute injection of CMI (10 or 20 mg/kg i.p.) was increased 2-fold after five chronic injections. Closely repeated injections gave a more marked effect than chronic administration, and daily administration was ineffective. The time course of the antinociceptive action correlated with that of blood and brain levels of CMI and its monodemethylated derivative. The enhancement of the antinociceptive action observed after chronic and closely repeated administration was shown not to be due to any modification of motor activity. It was suppressed by naloxone. Comparison with results reported in the literature shows the benefit of using a well-defined pattern of administration.

Analgesics↗
PubMed1987

Study of the clomipramine-morphine interaction in the forced swimming test in mice.

Tricyclic antidepressant-morphine interactions have been extensively studied on pain tests but less often on tests predictive of antidepressant activity. The effects of clomipramine (CMI) and morphine were tested on the forced swimming test in mice after pretreatment with CMI, morphine or saline. Like CMI, though less so, morphine was significantly active. Morphine pretreatment partially inhibited the effect of CMI irrespective of the morphine pretreatment dose, but reduction of morphine activity by CMI was non-significant. Acquired tolerance to morphine occurred, but not to CMI. The mechanisms at work were discussed. CMI and desmethylclomipramine (DCMI) plasma levels remained the same after morphine pretreatment, ruling out a pharmacokinetic mechanism. The interaction implied involvement of opiate systems. CMI might have been acting on two different opiate receptor populations, one sensitive to morphine pretreatment, the other not. The mechanism of this action seems to be different from that of morphine.

Animals↗
PubMed1986

Chronic administration of clomipramine inhibits morphine hot plate analgesia.

Clomipramine, chronically administered in mice, for 3 days, inhibits partially but significantly morphine analgesia in the hot plate test, when used at dose of 10 mg/kg/day, i.p.; 2.5 and 5 mg/kg/day were ineffective. Neither higher doses (20 and 40 mg/kg/day) nor longer duration of pretreatment (8 and 16 days) modified the intensity of this inhibition. Reduction in morphine analgesia was obtained after a 24h delay between the last injection of clomipramine and that of morphine (30 min before testing), while clomipramine did not induce any antinociceptive effect and clomipramine and desmethylclomipramine plasma and brain levels were low or undetectable. These results provide new evidence for the interaction between clomipramine and the endogenous opiate system. A pharmacokinetic interaction between clomipramine and morphine was excluded; involvement of change in opiate and 5 HT2 receptors by chronic administration of clomipramine is discussed.

Analgesia↗
PubMed1986

Effect of a short-term oral administration of cimetidine and ranitidine on the basal and thyrotropin-releasing hormone-stimulated serum concentrations of prolactin, thyrotropin and thyroid hormones in healthy volunteers. A double-blind cross-over study.

Cimetidine (400 mg b.d.), ranitidine (150 mg b.d.) and placebo were administered for 1 week to 6 healthy male volunteers in a randomized double-blind cross-over fashion. Hormonal concentrations before and after a TRH test were assessed before and after each treatment. A spontaneous decrease in the hormonal response to TRH was observed after placebo treatment. Both cimetidine and ranitidine induced a significant increase in basal prolactin (PRL) values. Neither TSH nor T3 were modified by cimetidine or by ranitidine. The basal concentration of reverse T3 was increased during cimetidine treatment. There was a significant rise in post-TRH T4 after cimetidine and ranitidine administration. These results suggest a role for histamine H2 receptors in the secretion of PRL and T4. Moreover, cimetidine affects the hepatic metabolism of thyroid hormones.

Adult↗
PubMed1986

[Diffusion of trimethoprim and sulfamethoxazole into the pleural fluid].

The level of Trimethoprim (TMP) and of Sulfamethoxazole (SMZ) in the fluid of both pleural effusion and plasma was determined in 7 patients on the first day of treatment consisting of two daily doses of 160 mg TMP and 800 mg SMZ. In 4 subjects, the levels were determined again on the third (J3) and fifth day of treatment (J5). Thus with TMP the ratio of pleural/plasma drug levels rose progressively from the first day of treatment to attain by 12 hours a mean value of 0.79 +/- 0.16; subsequently it stayed at about the same level for day 3 (J3) and day 5 (J5). As for SMZ, the ratio of the pleural plasma drug level reached a maximum at 8 hours on the first day of treatment (0.53 +/- 0.12) then rose progressively on day 3 (J3 0.58 +/- 0.06) and on day 5 to 0.71 (+/- 0.08). The levels of TMP in the pleural fluid were below those which are usually described in bronchial secretions. On the other hand those of SMZ are appreciably raised.

Drug Combinations↗
PubMed1985

Pharmacokinetics of the trimethoprim-sulphamethoxazole combination in the elderly.

The pharmacokinetics of a co-trimoxazole preparation (Bactrim Forte) containing trimethoprim (TMP) 160 mg and sulphamethoxazole (SMZ) 800 mg were determined in six young adults (29.3 +/- 4.4 s.d. years) and six elderly people (78.6 +/- 6.6 s.d. years). Following oral administration of a single dose, the pharmacokinetic parameters of SMZ and its N4-acetylated metabolite (N4SMZ) were similar in both groups. However Cmax of TMP was greater (2.06 +/- 0.29 s.d. vs 1.57 +/- 0.32 s.d. mg l-1; P less than 0.01) and its area under the curve was larger (34.30 +/- 6.98 s.d. vs 23.87 +/- 3.82 s.d. mg l-1 h; P less than 0.001) in elderly people than in younger subjects. Total clearance (CL/F) of TMP normalized to body weight was not significantly different in the two groups. There was no significant difference in serum protein binding of TMP and SMZ between the two groups. Urinary excretion of TMP, SMZ and N4SMZ was reduced by about 50% in the elderly compared to the young subjects. Renal clearance of TMP was significantly lower in the elderly group (19 +/- 10 s.d. vs 55 +/- 14 s.d. ml h-1 kg-1; P less than 0.001). Renal clearance of SMZ was not significantly different in the two groups. A study of plasma concentrations of TMP, SMZ and N4SMZ during continuous dosing in seven elderly patients treated for urinary or respiratory infections showed that steady state was reached after 3 days of treatment and that plasma drug concentrations were about two to three times higher than those observed after a single dose.

Acetylation↗
PubMed1985

Pharmacokinetics of ranitidine in acute upper gastrointestinal haemorrhage.

A pharmacokinetic study of ranitidine was performed in 14 patients with haematemesis divided into two groups according to the severity of blood loss. Pharmacokinetic values were calculated from plasma concentrations after the first of three daily injections (100 mg) and compared with those obtained in five healthy volunteers (50 mg i.v.). There were no significant differences between patients in the two haemorrhage groups and controls. The low, or even questionable, effectiveness of histamine H2-receptor antagonists in the treatment of upper gastrointestinal haemorrhage does not seem to be due to pharmacokinetic factors.

Acute Disease↗
PubMed1984

Reverse-phase liquid chromatography and pharmacokinetic study of two hydroxylated analogues of quinidine in dogs.

Two hydroxylated analogues of quinidine with antiarrhythmic properties, 3S-hydroxyquinidine and 3R-hydroxydihydroquinidine were assayed by reverse-phase high-performance liquid chromatography. The analytical technique uses plasma protein precipitation and direct injection on a C18 column, with an isocratic mobile phase and spectrofluorometric detection. 3R-Hydroxyquinidine is employed as the internal standard. Linearity is verified up to 5 mg/L for the two drugs; concentrations between 0.5 and 2.5 mg/L were measured with a CV of 0.5-2.07% for a given day and a sensitivity limit of 50 micrograms/L. Plasma concentration-time profiles and pharmacokinetic parameters in three dogs are presented after intravenous or oral administration. A significant difference is observed in terminal half-life, terminal rate constant, and total clearance of the two polar analogues of quinidine.

Administration, Oral↗