Lack of correlation between plasma levels of amitriptyline (and nortriptyline) and clinical improvement of chronic pain of peripheral neurologic origin.
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Adult↗
Biomedical subjects
M A Tran
Publications and source records attributed to M A Tran.
Effect of clonidine on adrenal medulla catecholamine levels in rats.
The effects of clonidine on adrenal medulla catecholamines levels were studied in normotensive rats. Intraperitoneal injections (50,100 micrograms/kg) of clonidine caused a dose-dependent decrease in adrenaline content of the gland. This effect was suppressed by denervation of the adrenal medulla, i.e. unilateral section of splanchnic fibers performed 5 days before. These results demonstrate that clonidine decreases the catecholamine content of the adrenal medulla only through a central action. They suggest that the adrenal medulla is involved in the hypotensive effect of clonidine.
Adrenal Medulla↗
A study of the action of clonidine on secretion from the adrenal medulla in dogs.
The effects of clonidine on adrenal catecholamine (adrenaline and noradrenaline) secretion were investigated in chloralose-anaesthetized dogs. Intravenous administration of clonidine (10 and 20 micrograms kg-1) induced a decrease in both adrenal catecholamine secretion rates and cardiovascular parameters (blood pressure and heart rate). In contrast, a dose of 5 micrograms kg-1 was ineffective. Intracisternal clonidine (in a lower dose of 3 micrograms kg-1) also decreased adrenaline and noradrenaline release from the adrenal gland. Clonidine failed to modify adrenal catecholamine release evoked by electrical stimulation of the splanchnic nerve. These results demonstrate that clonidine decreases adrenaline release from the adrenal gland through a central and not a peripheral mechanism in dogs. This action might contribute to its antihypertensive effects.
Adrenal Medulla↗
Experimental and clinical approaches to treatment of hypertension by dopamine receptor agonists.
The action of several dopamine agonists on blood pressure was investigated. In dogs, apomorphine induced a decrease in blood pressure and an increase in heart rate. These effects were suppressed by intravenous haloperidol or phentolamine. Intravenous but not intracisternal domperidone suppressed the hypotensive responses elicited by intravenous or intracisternal apomorphine. Furthermore, the hypotensive effect of bromocriptine or apomorphine was abolished in adrenal demedullated dogs. Apomorphine and bromocriptine decreased adrenal catecholamine levels. In men, the acute hypotensive property of apomorphine (but not the long term effect of bromocriptine) was suppressed by pretreatment with domperidone. In hypertensive Parkinsonians, bromocriptine reduced blood pressure, induced an increase in inulin clearance, a decrease in plasma creatinine concentration and in renal vascular resistances. These results suggest that dopamine agonists (like apomorphine or bromocriptine) reduce blood pressure through both a decrease in sympathetic tone and an improvement in renal function. However, the mechanism of the acute and long term hypotensive effects could be different only involving peripheral mechanisms after acute administration and both peripheral and central structure under chronic treatment. In addition, preliminary results suggesting the potential interest of dopamine antagonists in the management of orthostatic hypotension are discussed.
Dopamine↗
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.
Chronic Disease↗
[Effects of a morphine-clomipramine combination on a test of experimental analgesia].
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.
Analgesics↗
Studies on the cardiovascular actions of apomorphine in dogs: central versus peripheral mechanisms and role of the adrenal medulla.
The effects of apomorphine on blood pressure and heart rate were studied in normotensive chloralose anaesthetized dogs. Intravenous apomorphine (200 micrograms/kg) induced both a marked decrease of blood pressure and an increase in heart rate. These two cardiovascular responses to intravenous apomorphine were suppressed by haloperidol (1 mg/kg i.v.) or phentolamine (1 mg/kg i.v.). In contrast, pretreatment with atropine (1 mg/kg i.v.) only abolished the chronotropic (but not the hypotensive) response to apomorphine. Intravenous (500 micrograms/kg) but not intracisternal (50 micrograms/kg) domperidone suppressed the hypotensive responses elicited by intravenous or intracisternal apomorphine. In contrast, domperidone, injected either by intravenous or intracisternal route, abolished apomorphine-induced tachycardia. In adrenal demedullated dogs, the hypotensive response to apomorphine was abolished. These results suggest that the hypotensive response to apomorphine in normotensive dogs is mainly mediated by activation of peripheral dopaminergic mechanisms. The drug decreases blood pressure through stimulation of dopaminergic receptors located on sympathetic nerve terminals and on the adrenal medulla leading to a decrease of the release of catecholamines.
Adrenal Medulla↗
Interplay of alpha-2 and beta adrenoceptors in the control of free fatty acid release from bone marrow adipose tissue.
The effect of various adrenergic drugs on the free fatty acid (FFA) output from bone marrow was studied in dog tibia after constant flow autoperfusion of the nutrient artery by femoral arterial blood and cannulation of the nutrient vein. Clonidine, an alpha-2 adrenoceptor agonist, inhibited the isoproterenol-induced FFA outflow from bone marrow adipose tissue. This effect was suppressed by the alpha-2 antagonists (phentolamine and yohimbine). Moreover, clonidine inhibited the FFA outflow initiated by theophylline associated with adenosine deaminase. When the alpha-2 sites were blocked by phentolamine or yohimbine, epinephrine exerted an enhanced effect on FFA outflow in comparison with its effect when infused alone. These in vivo experiments clearly demonstrate that alpha-2 adrenoceptor stimulation is able to inhibit beta-stimulated or theophylline plus adenosine deaminase-promoted lipid mobilization from bone marrow fat stores. The simultaneous stimulation of alpha-2 and beta adrenoceptors initiated by epinephrine could be responsible for the weaker lipid-mobilizing effect of the endogenous catecholamine. It is concluded that adrenoceptors are operative in bone marrow adipose tissue and control FFA outflow in physiological conditions. Moreover, the existence of an interplay between alpha-2 and beta adrenergic effects in in vivo conditions is demonstrated.
Adenosine Deaminase↗
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.
Analgesics↗
[Pharmacological basis for the therapeutic use of ergot alkaloids].
The main mechanisms of action of ergot alkaloids are discussed. Their clinical use (migraine, uterine haemorrhage, orthostatic hypotension, senile cerebral insufficiency, hyperprolactinaemia or Parkinson's disease) and their adverse effects are explained by an affinity for three kinds of central and peripheral receptors: alpha adrenergic, serotoninergic or dopaminergic receptors.
Adrenergic alpha-Agonists↗
[Analgesic properties and plasma concentrations of clomipramine in chronic pain].
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.
Adult↗
In vivo alpha 2-adrenoceptor-mediated inhibition of isoproterenol-stimulated free fatty acid output in dog bone marrow adipose tissue.
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Adipose Tissue↗
Effects of catecholamines on free fatty acid release from bone marrow adipose tissue.
We have studied the effect of epinephrine and isoproterenol on free fatty acid (FFA) mobilization from bone marrow adipose tissue in dog tibia after constant-flow autoperfusion of the nutrient artery by ipsilateral femoral arterial blood. The perfusions of epinephrine (0.025 microgram/min) or isoproterenol (0.005 microgram/min) significantly increased the FFA level in the nutrient vein of the tibia. Moreover, our data demonstrate that in vitro the bone marrow adipose tissue was less responsive to catecholamines than omental adipose tissue. It can be concluded that bone marrow adipose tissue is able to release FFA after administration of catecholamines but to a lesser extent than in other adipose tissue (omental adipose tissue). These results support the hypothesis that the bone marrow adipose tissue is involved in local nutrition rather than in the total energy supply of the animal.
Adipose Tissue↗
The effect of lumbar sympathetic stimulation on the vasculature of bone.
1 The nutrient artery to the tibia of anaesthetized dogs was perfused at a constant rate by blood from the femoral artery and the perfusion pressure in the artery, the intramedullary pressure of the bone and the pressure in the nutrient vein recorded. 2 Low frequency stimulation (1 to 5 HZ) of the lumbar sympathetic chain always increased the perfusion pressure but the intramedullary pressure sometimes increased, sometimes decreased and sometimes remained unchanged. 3 The alpha-adrenoceptor blocking agents, phentolamine (1 mg/kg i.v.) and dihydroergotamine (0.5 mg/kg i.v.) reduced or abolished these effects whereas the beta-adrenoceptor blocking agent, propranolol (1 mg/kg i.v.) did not modify them. 4 The nutrient vein end pressure did not differ significantly from the intramedullary pressure and underwent similar variations during stimulation of the lumbar sympathetic chain.
Adrenergic alpha-Antagonists↗
The influence of some vasoactive drugs on bone circulation.
We have studied the effect of various drugs on the intramedullary pressure in dog tibia after constant-flow autoperfusion of the nutrient artery by femoral arterial blood. The perfusion pressure and carotid arterial pressure were also recorded. Isoprenaline, acetylcholine, histamine, theophylline always lowered the perfusion pressure but had a variable effect on intramedullary pressure. This results from several factors e.g., perfusion pressure and intraosseous vasomotoricity. Adrenaline always caused a rise of the perfusion pressure and lowered the intramedullary pressure in most of the cases. Such effects were reduced or suppressed by alpha-blocking drugs. Isoprenaline caused a lowering of the perfusion pressure which was suppressed by propranolol. A rise of the intramedullary pressure through beta-induced vasodilatation was shown in some experiments. The effect of adrenaline on the perfusion pressure could be reversed after alpha-blockade. These results show the presence of intraosseous vascular alpha- and beta-adrenoceptors.
Acetylcholine↗
[Effect of pindolol on experimental hypertension in the dog. Comparison with propranolol, practolol, oxprenolol, bupranolol, alprenolol and butoxamine].
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Adrenergic beta-Antagonists↗
A study of the oxygenation of trochanteric bone blood and its correlation with the maximum intra-medullary pressure value in 85 cases of chronic coxopathy.
The authors carried out measurements of the gases (pH, PCO2, PO2, SaO2) on blood from the trochanter of 85 chronic hip diseases in 73 patients. Simultaneous measurements were made on the arterial blood and on the blood of the femoral vein of the same side. A statistically significant difference in blood PO2 and oxygen saturation between the group of necrosis of the femoral head and the group of osteoarthritic hips was found. There is a paradoxical oxygen hypersaturation in case of necrosis. This hypersaturation is observed to parallel the increase of the intramedullary pressure in the same bone area.
Carbon Dioxide↗
[Influence of variations in blood pH on the bronchodilator action of salbutamol and terbutaline].
In the cat, the broncho-dilatator effects of salbutamol and terbutaline are influenced by blood pH variations. Gazeous or metabolic alkalosis increases, acidosis decreases, the broncho-dilatation provoked by salbutamol or terbutaline.
Acidosis↗