Acute release of catecholamines on circulating blood cell adrenoceptors and metabolic indices in dog.

The effects of acute release of endogenous catecholamines on both platelet alpha 2 and leukocyte beta adrenoreceptors and metabolic indices (glucose and free fatty acids) were investigated in dogs by means of a model of neurogenic hypertension following acute sinoaortic denervation (ASAD). Despite the marked increase in catecholamine levels (+4.2-fold for noradrenaline and 16.7-fold for adrenaline, for example, at minute 45 following ASAD) and in glucose plasma levels, and the significant decrease in free fatty acid plasma levels, no change in platelet alpha 2 or leukocyte beta adrenoreceptor binding sites (number as well as affinity) was observed during the whole experiment. It is suggested that the number of platelet alpha 2- and leukocyte beta-adrenoreceptors is not submitted to short-term regulation, at least by endogenous catecholamines in dogs.

Measurement of plasma levels of clomipramine in the treatment of chronic pain.

The analgesic effect of clomipramine and the possible relationships between the antalgic action and the plasma levels of this tricyclic drug have been studied in 30 patients with chronic pain induced by nervous lesions determining a deafferentation. Twenty of 30 patients treated with clomipramine reported a significant improvement (up to 50%) observed as soon as the 4th day, with few side effects. The pharmacokinetic analysis shows the existence (r = 0.358; p less than 0.001) of a relationship between analgesia and plasma levels of clomipramine for each individual patient. This study also indicates a "therapeutic window" of plasma levels between 20 and 85 ng/ml. These results permit discussion of measurement of plasma levels of clomipramine in the treatment of chronic pain.

Is there any relationship between antinociception, doses and plasma levels of clomipramine during subchronic treatment in rats?

The antinociceptive effects and the plasma levels (evaluated by high liquid pressure chromatography) of clomipramine during a subchronic (5 days) treatment were studied in rats using the Nilsen's test. Clomipramine (10, 20, 30 and 40 mg/kg administered by mouth) showed a clear dose-dependent analgesic effect. The study of the partial correlation coefficients did not found a relationship between plasma levels and antinociception under our experimental conditions. These results suggest that regular monitoring of plasma levels of clomipramine appears to be useless in the treatment of patients with chronic pain.

Lymphagogue and pulsatile activities of Daflon 500 mg on canine thoracic lymph duct.

An earlier report proved that Daflon 500 mg constituted of 90% diosmin and 10% hesperidin exerts a lymphagogue effect on dogs. The aim of the present work is to investigate whether the lymphagogue effect of Daflon 500 mg is associated with an increase in pulsatile activity of lymphatic vessels. The investigation was carried out on mongrel dogs anaesthetised by pentobarbital (10 mg/kg); the lymph was collected by a fistula on the thoracic lymphatic duct; using this fistula the pulsatile activity of lymphatic vessels was estimated by Campbell and Health methodology. The lymphatic volume was measured every ten-minutes in graduated tubes for 2 hours and the pulsatile component of intralymphatic pressure (MPC) was estimated from measurements of the area (expressed in mm2) enclosed by the part of the tracing due to the pulsatile component during one minute. Daflon 500 mg was intravenously injected after having been dissolved in DMSO + TRIS; three doses were injected: 12.5, 6.25 and 3.125 mg/kg. Regarding the lymphagogue effect, Daflon 500 mg induced an increase in lymphatic flow correlated with the administered doses. The maximal 10-minute period lymphatic flows were 191% (12.5 mg/kg), 171% (6.25 mg/kg) and 91% (3.125 mg/kg); the peak of the effect was, in each case, reached between 20 and 25 minutes after the injection. Regarding the pulsatile activity, Daflon 500 mg induced an increase of MPC. The MPC was correlated with the increase in lymph flow (r = 0.877).

[Effects of a morphine-clomipramine combination on a test of experimental analgesia]. / Effets de l'association morphine-clomipramine sur un test d'analgésie expérimentale.

Morphine (2.5 mg/kg sc) i.e. at a non-antinociceptive dose, augmented clomipramine-induced antinociceptive effect but failed to alter the values of clomipramine (10, 20, 40 mg/kg orally) levels in rats. These results suggest that the potentiation of clomipramine-induced analgesia by morphine does not result from a peripheral pharmacokinetic mechanism but probably involves a central interaction between clomipramine and opiates pathways.

[Analgesic properties and plasma concentrations of clomipramine in chronic pain]. / Etude des proprétés analgésiques et des concentrations plasmatiques de clomipramine dans les douleurs chroniques.

The analgesic effect of clomipramine and the possible relationships between the antalgic action, the doses and the plasma levels of this tricyclic drug have been studied in 15 patients with chronic pain induced by nervous lesions determining a deafferentiation. Eight of 15 patients treated with clomipramine (100 mg/IV during 10 days and then 150 me per os) reported a significant improvement (up to 50 per cent during 3 to 18 months). The study of the partial coefficients of correlation did not show a relationship between plasma levels and analgesia in the total population or in the subgroup of the 8 improved patients. These results confirm the analgesic properties of clomipramine and suggest that regular monitoring of plasma levels of clomipramine does not appear of practical interest in the treatment of chronic pain.

[Initial results of a pharmacokinetic study of pipothiazine and its palmitic ester (Piportil L4) in a schizophrenic population]. / Premiers résultats d'une étude pharmacocinétique de la pipotiazine et de son ester palmitique (Piportil L4) dans une population de schizophrènes.

Plasma kinetics of pipotiazine have been studied in ten schizophrenic patients after oral administration of single dose of pipotiazine at 7 a.m. (30 mg, drops). Peak plasma concentrations are reached one hour after administration (41.8 +/- 19,9 ng/ml) and then rapidly decline until 24 h (2.2 +/- 1.2 ng/ml). During the following days plasma concentrations remain stable at the same sampling times. After 3 days wash-out and first intramuscular injection of pipotiazine palmitate (100 mg) main pharmacokinetic data are found: plasma concentrations of pipotiazine are not detectable during at less 3 days after injection, maximal drug level is attained during second week after i.m. (1.7 +/- 0.9 ng/ml). A period of decline is then recorded. Furthermore the mean ratio between pipotiazine plasma concentration after oral and i.m. administration is about 20. When pipotiazine palmitate is given every fourth week, steady state seems to be reached as early as the second month.