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Biomedical subjects

J Fialip

Publications and source records attributed to J Fialip.

At least 55 records · Page 3Linked to original sources
PubMed1988

An automated method to analyze vocalization of unrestrained rats submitted to noxious electrical stimuli.

Unrestrained rats were subjected to electrical stimuli applied to their paws via an electrified cage floor. Intensity, duration, and order of stimulation were chosen after preliminary tests. Vocalization threshold and vocalization as a behavioral response were studied. The vocalization was recorded and the signal analyzed by a simple computerized method that calculated five parameters: delay, maximal amplitude, duration, area, and maximal derivative with respect to time. The last four parameters increased with increasing intensity of stimulation and remained stable when the same stimulation was given repeatedly. Sensitivity to morphine (2.5 and 5 mg/kg s.c.) was tested. Morphine raised the threshold and lowered vocalization parameters, and it was antagonized by naloxone, thus validating the method. The sensitivity of the test and its capacity to separate sensory and affective components of pain are discussed.

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↗
PubMed1987

Benzodiazepine withdrawal seizures: analysis of 48 case reports.

Various reactions to benzodiazepine withdrawal have been widely described. Among these, seizures have occasionally occurred on abrupt withdrawal. Our own experience of 48 cases of seizures suspected to have been caused by benzodiazepine withdrawal and reported to the Adverse Drug Reaction (ADR) Monitoring Center (1979-1985) showed that a great variety of benzodiazepines with different half-lives were involved, those most frequently implicated being the most widely prescribed. The occurrence of seizures was not always related to the interruption of long-term treatment (from a few days to greater than 7 years) nor to high-dose treatment, the range of dosages being usually close to that recommended. However, in some cases, several benzodiazepines had been taken simultaneously. The time between the last intake of the drug(s) and the occurrence of the seizures was shorter when a short-life benzodiazepine had been used. Additional factors were frequently involved; these factors were present in 29 cases and were multiple in nine of them. The incidence of withdrawal seizures was related more to the presence of these additional factors than to either the pharmacokinetics of the drugs or the pattern of treatment.

Adult↗
PubMed1987

[Synthesis and pharmacologic evaluation of some dihydropyran carboxylic acids].

The synthesis of three new dihydropyran carboxylic acids has been performed by uncommon procedures: cyanosilylation, cyclisation of oxime. Their chemical structure was confirmed by I.R. and N.M.R. data. In a pharmacological evaluation they were found to possess significant effects on the passive cutaneous anaphylaxis test and on the central nervous system; one of them showed an interesting antiallergic effect whilst another showed an interesting sedative effect.

Analgesics↗
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↗
PubMed1985

[Calcium and phosphorus metabolism in insulin dependent and non-insulin dependent diabetics, well-controlled and poorly-controlled].

We studied phosphorus and calcium metabolism in 50 adult insulin dependent and non insulin dependent diabetics arranged in 4 groups according to therapy and control of diabetes. We observed: a low level of blood magnesium in all diabetics a lower level of P T H, more pronounced with poorly controlled diabetes. a decrease of 1-25 (OH) 2 D levels without modification of the 25 (OH) D levels in badly controlled diabetics. This decrease may be related to the low level of PTH with a 1 alpha hydroxylation defect. These results are in favor of the hypothesis of a primary bone problem leading to the pre-senile and subclinical osteoporosis observed in diabetics. Hyperglycaemia rather than insulinopenia may be involved. Rigorous diabetes control significantly decreases all the observed differences, except the low magnesium level.

Adult↗
PubMedDate not supplied

Plasma and brain pharmacokinetics of amitriptyline and its demethylated and hydroxylated metabolites after acute intraperitoneal injection in mice.

The fate of amitriptyline (AMI) and its demethylated and hydroxylated metabolites was studied in Swiss CD1 mice, after acute intraperitoneal injection of AMI (20 mg/kg). Levels of each compound were determined to establish pharmacokinetic parameters in plasma and brain. Absorption and elimination of AMI were rapid (tmax = 0.37 h and 0.42 h, and t1/2 = 3.2 h and 3.6 h in plasma and brain, respectively). In plasma, 10-OH-nortriptyline was the main metabolite (46% of AUC) and 10-OH-amitriptyline reached significant levels but only during the first hour. In brain, AMI (43% of total AUC), nortriptyline (NOR) (29%) and demethylnortriptyline (DM-NOR) (11%) were the most abundant compounds, possibly through high blood-brain barrier transfer and/or marked intracerebral demethylation. Brain OH-metabolite levels were much lower. Knowledge of kinetic parameters and metabolism of AMI can help in the evaluation of pharmacological activity.

Amitriptyline↗
PubMedDate not supplied

[Follow-up of elderly patients after emergency hospitalization for severe drug reactions].

Forty-one observations concerning persons aged over sixty-five hospitalized for adverse drug reactions in the Emergency Service of Clermont-Ferrand University Hospital were collected and analysed by the Adverse Drug Reaction Monitoring Centre. The symptoms were predominantly haemorrhage, particularly digestive, connected with the use of oral anticoagulants, salicylates and anti-inflammatories. The follow-up of the thirty-one most severe cases (hospitalization over 48 h and/or initial resuscitation) was undertaken in hospital and other care centres. In seventeen cases, complications occurred linked to the hospitalization (especially infections and neuropsychic complications) or to the adverse reaction itself through the measures taken to correct it (particularly cardiovascular complications). The hospitalization revealed hitherto undetected conditions in twelve patients, thereby allowing the prognosis to be improved. This positive side hardly outweighs the detrimental effects of adverse drug reactions in elderly subjects (six deaths and four irreversible incapacitations). Thus vital and social prognosis of elderly appears greatly damaged by adverse drug reactions.

Aged↗
PubMedDate not supplied

[Salsolinol, an endogenous molecule. Possible implications in alcoholism, Parkinson's disease and pain].

Salsolinol can be formed either by condensation of dopamine with acetaldehyde, or by condensation of dopamine with pyruvic acid followed by decarboxylation. Salsolinol has a complex pharmacologic profile. Its opium-like activity may be related to alcohol dependency and to the effectiveness of naloxone during acute alcohol intoxication. Because they had noticed that alcoholism and Parkinson's disease rarely coexist, the authors undertook a study to confirm this fact and attempt to explain it by implicating salsolinol. Urinary excretion of salsolinol was found to increase following ingestion of alcohol, as well as in Parkinson patients under L-dopa treatment. The authors also found that urinary salsolinol was very low in untreated patients with Parkinson's disease. Salsolinol was detected in a number of foods and beverages. Separate assays of enantiomeres showed that the S enantiomere predominates in some foods whereas the R enantiomere is more abundant in humans. Lastly, the antinociceptive effects of salsolinol and its enantiomeres were studied in mice and antidepressant effects were evidenced using predictive tests.

Aged↗
PubMedDate not supplied

Lack of importance of caffeine as an analgesic adjuvant of dipyrone in mice.

The analgesic effect of caffeine used alone and in combination with dipyrone and butalbital was evaluated after oral administration in mice, using two different pain tests: the hot plate test and the phenylbenzoquinone-induced writhing test. Neither caffeine (5 to 200 mg/kg) nor butalbital (10 and 20 mg/kg) (20 mg/kg was the highest dose that did not induce sleep) produced a significant antinociceptive effect, whereas dipyrone was active from 400 mg/kg in the hot plate test and from 50 mg/kg in the writhing test. The scores obtained with the combinations were not different from those of the dipyrone-treated group, except for the butalbital-dipyrone combination. Thus caffeine is not an analgesic adjuvant in mice; its presence in the combination studied appears to be justifiable only insofar as it inhibited the sedative effect of butalbital.

Aminopyrine↗