PubMed Health⌕ Search

Biomedical subjects

A Galiano

Publications and source records attributed to A Galiano.

16 recordsLinked to original sources
PubMed2002

Electrophysiologic cardiac effects of the new local anesthetic IQB-9302 and of bupivacaine in the anesthetised dog.

BACKGROUND: Local anesthetics are not free from potentially fatal complications. Therefore every new local anesthetic should be tested to demonstrate a lower, or at least similar, degree of toxicity over clinically used analogs. Most toxic effects from local anesthetics affect the cardiac electrophysiologic function, so the aim of this study was to characterize the electrophysiologic effects of a new long-acting local anesthetic (IQB-9302, Ciprocaine), and compare them with those of bupivacaine in the anesthetized dog. METHODS: Eight Beagle dogs received three increasing infusion doses of either IQB-9302 or bupivacaine. Under isoflurane anesthesia, dogs were instrumented to monitor cardiovascular (cardiac output, arterial and venous blood pressures) and cardiac electrophysiologic data (sinus and atrioventricular (AV) node function, atrial, nodal and ventricular conduction times, and refractoriness). RESULTS: Only the highest dose of both drugs induced hemodynamic or electrophysiologic alterations: cardiac output and heart rate were reduced while blood pressures remained unchanged. Atrial and intranodal conduction times and atrial refractoriness increased similarly with both anesthetics, but to a slightly lesser extent with IQB-9302. Significant increases in His-Purkinje and intraventricular conduction times were the most severe noxious effects and occurred only with large doses of either drug. IQB-9302 was slightly less toxic than bupivacaine and, unlike this latter drug, potentially fatal arrhythmias were not induced. CONCLUSION: IQB-9302 has hemodynamic and cardiac electrophysiologic effects similar to those caused by bupivacaine. Nevertheless, slightly less toxic effects were derived from IQB-9302 administration than with bupivacaine, and, unlike the latter, the former might be less proarrhytmogenic. The new long-acting local anesthetic IQB-9302 may offer clinical advantages compared with bupivacaine.

Anesthetics, Inhalation↗
PubMed2001

Ulnar nerve block induced by the new local anesthetic IQB-9302 in healthy volunteers: a comparison with bupivacaine.

UNLABELLED: We evaluated the duration of sensory anesthesia after blockade of the ulnar nerve of IQB-9302, a new local amide anesthetic, compared with bupivacaine. A double-blinded, randomized, cross-over study in 12 healthy volunteers aged 18 to 35 yr was performed. Three milliliters of 0.25% IQB-9302 was administered in one wrist and bupivacaine in the other. A week later, the blocks were repeated with a concentration of 0.5%. These concentrations were chosen because they seemed to be equipotent in previous studies. The duration of sensory anesthesia was the main variable measured; secondary outcomes were motor block, time to onset, and time to recovery from block. The duration of sensory block was similar for IQB-9302 and bupivacaine at a concentration of 0.25%; median and range: 409 min (0-800 min) for IQB-9302 and 258 min (0-665 min) for bupivacaine (95% confidence interval for the difference from -47 to 545, P = 0.82, Wilcoxon's test). The results with 0.5% were: 525 min (440-735 min) and 690 min (365-1098 min), respectively (P = 0.026). There were no significant differences in the other variables measured. No important adverse reactions were seen. We conclude that IQB-9302 is an effective new local anesthetic for blockade of ulnar nerve at the concentrations tested. IMPLICATIONS: IQB-9302 is a new local anesthetic that has shown a long duration of action and low cardiovascular toxicity in preclinical studies. We report the results of a phase I clinical trial to compare this new drug with bupivacaine for ulnar nerve block.

Adolescent↗
PubMed1994

Anti-ischaemic and haemodynamic effects of elgodipine, a potent new generation calcium antagonist, in chronic stable angina.

The effects of oral elgodipine, a new dihydropyridine calcium antagonist on ischaemia and left ventricular function were assessed by a single blind placebo controlled study in 12 patients with chronic stable angina. Graded treadmill exercise and echocardiography/Doppler were performed before and 90 min after single oral doses of elgodipine of 20 mg, 40 mg and 60 mg, or placebo, given at weekly intervals. Elgodipine significantly increased exercise time by 1.1, 2.0 and 2.4 min, (P < 0.001 in each case) and time to onset of angina by 1.1 (P < 0.01), 1.9 (P < 0.001) and 2.6 min (P < 0.001) with increasing doses of the drug. Angina was abolished in 50% of patients with significant improvement in ST depression at peak exercise (P < 0.001) with the 60 mg dose. Blood pressure fell significantly at rest and peak exercise with a corresponding significant increase in heart rate. Ejection fraction was increased by 7.8% (P < 0.001) and 8.4% (P < 0.001) as was the stroke volume by 9.3 ml (P < 0.001) and 12.5 ml (P < 0.001) at 40 mg and 60 mg respectively. Peak mitral A to E velocity ratio and total peripheral resistance decreased significantly in a dose related linear trend. Only minor side effects were noted and no patient required withdrawal from the study. The results demonstrate that oral elgodipine is a potent anti-ischaemic agent. An improvement in the echocardiographic parameters of left ventricular systolic and diastolic function was also seen.

Aged↗
PubMed1994

Effects of oxodipine and elgodipine on (+)-[3H]-isradipine binding to cardiac and vascular membranes: cardiovascular selectivity.

We studied the effects of six dihydropyridines on the specific binding of (+)-[3H]-isradipine to vascular (portal vein) and cardiac isolated membranes to achieve the relative cardiovascular selectivity of these compounds. Elgodipine, (+)-oxodipine and nifedipine had a significantly higher affinity for the vascular L-type calcium channel than for the cardiac calcium channel while nicardipine showed opposite properties. The other dihydropyridines (nitrendipine and (+)-isradipine) had similar affinities for the cardiac and vascular calcium channels. As the membrane potential of isolated membranes is about 0 mV, these results suggest that the differences in binding of these dihydropyridines to L-type calcium channels in vascular and cardiac cells may be attributed to differences in the molecular structure of these calcium channels.

Animals↗
PubMed1994

Electrophysiological and radioligand binding studies of elgodipine and derivatives in portal vein myocytes.

The effects of a novel dihydropyridine, elgodipine, and of three derivatives have been studied on the calcium channel currents of isolated cells from rat portal vein by the patch-clamp technique, and on specific (+)-[3H]isradipine binding to vascular membranes. Elgodipine inhibited both T- and L-type calcium channels in a concentration-dependent manner. Half-inhibitions of T- and L-type calcium channel current were obtained at concentrations of 32 and 2.3 nM, respectively. Currents activated repetitively were similarly inhibited than those after a rest period, indicating absence of use-dependent inhibition by elgodipine. When cells were held at depolarized membrane potentials at which T- or L-type calcium channels were inactivated, the inhibitory effects of elgodipine were enhanced on both calcium channel currents, indicating that the elgodipine-induced inhibition was voltage-dependent. The elgodipine concentration which blocked the inactivated calcium channels were 5 to 7 times lower than those which blocked the resting calcium channels. The inhibition constant for elgodipine obtained from the displacement of (+)-[3H]isradipine binding to the L-type calcium channels in vascular membranes was identical to the dissociation constant calculated from electrophysiological data on inactivated calcium channels. At concentrations that completely inhibited calcium channels, elgodipine had no effect on chloride and potassium channels, and did not interfere with the intracellular calcium stores.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Study of pharmacokinetics and pharmacodynamics of two preparations of metoclopramide.

A pharmacokinetic-pharmacodynamic cross-over study in a group of volunteers (8 male, 4 female) was performed to evaluate the activity and plasma levels of a new sustained-release metoclopramide (CAS 364-62-5) formulation (Cronoprimperan) in comparison to a standard formulation (Primperan). During the course of this trial volunteers on both medications complained of mild to moderate adverse effects as headaches and drowsiness. Elevated monocyte counts were seen in all volunteers at the end of the study without determinable relationship to the medications. No relevant differences were observed between the two preparations in the standard motor and coordination tests. The new sustained-release metoclopramide formulation showed 12-h coverage with a plateau shaped form for achieving constant blood levels throughout the day without reaching blood concentrations above clinically tolerable limits.

Adolescent↗
PubMed1992

The fate of altered hepatocytic foci as a result of treatment with oxodipine, a calcium channel blocker.

The dietary administration of the calcium channel blocker oxodipine to Fischer (F344) rats for 12 and 30 months resulted in increased incidence of altered hepatocytic foci (AHF). As the Environmental Protection Agency (EPA) regards AHF as potentially precancerous it is important to accumulate experimental evidence which may negate this theory. In the case of oxodipine we proved that with dosages close to maximum tolerated dose (MTD) for prolonged periods no hepatic neoplasms were produced. The possible nature of such AHF is discussed.

Alkaline Phosphatase↗
PubMed1992

Thickening of the adrenal zona glomerulosa in dogs induced by oxodipine, a calcium channel blocker.

Subchronic effects of oxodipine, a calcium channel blocker affecting the adrenal gland of the dog, are described. Thirteen wk of treatment at a high dose (24 mg/kg/day) of oxodipine resulted in drug-induced thickening of the zona glomerulosa and increased stimulation of its secretory activity. It is postulated that subchronic administration of oxodipine at this dosage resulted in a decrease in blood pressure, with uninterrupted stimulation of the adrenal zona glomerulosa to release aldosterone, causing an increase in the width of this portion of the gland involving cellular hyperplasia. Support for this indirect effect is found in the increased presence of renin granules in the juxtaglomerular apparatus.

Adrenal Glands↗
PubMed1990

Gingival hyperplasia in rats induced by oxodipine--a calcium channel blocker.

Oxodipine, a new calcium channel blocker, induced gingival hyperplasia in rats. This is the first time that a calcium channel blocker has been documented as resulting in gingival hyperplasia in rats. In contrast to diphenylhydantoin, the hyperplastic changes induced by oxodipine were not precipitated by any prior irritation. The histology consisted of purely fibroblastic proliferation without infiltrate of inflammatory cells.

Animals↗
PubMed1990

Drug-induced decrease of serum alanine and aspartate aminotransferase activity in the rat, as a result of treatment with oxodipine, a new calcium channel blocker.

Chronic oral administration of oxodipine, a new calcium channel blocker, resulted in a reduction in the blood enzyme activity of alanine and aspartate aminotransferase. The reductions were both time and dose related. The decline in enzyme activities was accompanied by microscopic hepatic changes, which in the opinion of the authors should have been associated with an increase in the enzyme activities of alanine aminotransferase and aspartate aminotransferase. The effect was only partially reversed one month after the cessation of oxodipine treatment.

Alanine Transaminase↗
PubMed1988

Gingival hyperplasia in dogs induced by oxodipine, a calcium channel blocking agent.

Subchronic oral exposure of dogs to Oxodipine, a new calcium channel blocker of the dihydropyridine-type, resulted in dose-related gingival hyperplastic changes. The doses at which an effect was elicited were 24 and 73 times the intended therapeutic dose for man. The effects were first noted after 7 weeks of treatment, and were limited to the high and intermediate dose groups of both sexes. Macroscopically, a generalized enlargement of the maxillary and mandibular facial and lingual gingivae were noted. The histological changes were similar to those described in man for Nifedipine and hydantoin-related drugs. An increase in the activity of alkaline phosphatase and a decrease in alanine aminotransferase was demonstrated. This article is the first to describe gingival hyperplasia in dogs induced in a dose-dependent manner by a calcium channel blocker.

Alanine Transaminase↗
PubMed1986

Pharmacological study of the new mucolytic drug N-guanyl-cysteine.

The pharmacological evaluation of N-guanyl-cysteine (IQB-782) is reported. This new cysteine derivative shows a potent mucolytic-expectorant activity in different test systems. Thus, IQB-782 protects rats against tobacco-smoke-induced respiratory airway obstruction, increases the tracheo-bronchial mucus secretion in rabbits and increases the pulmonary excretion of fluorescein in mice, an index of broncho-secretagogue activity. Like other mucolytics, IQB-782 is also effective in vitro in reducing the viscosity of a suspension of gastric mucin. This new drug is apparently devoid of any cardiovascular or autonomic activity and shows a moderate CNS depressant effect. IQB-782 is consequently a new thiol derivative which may offer some advantages in the treatment of different types of obstructive pulmonary disease.

Animals↗
PubMedDate not supplied

Constipation and megacolon in rats related to treatment with oxodipine, a calcium antagonist.

The constipatory effects of oxodipine, a dihyrdopyridine-type calcium antagonist, have been described in a 3-mo, 12-mo, and 30-mo feeding toxicity study in rats. This paper reports the occurrence of megacolon in rats as a result of the constipatory effects of chronic administration of oxodipine. The first mortality due to oxodipine was seen after about 1 yr of treatment at a dose of 225 mg/kg/day. The toxic effects noted were dose-, time-, and sex-related. Female rats appeared more sensitive to the constipatory effects of the drug. The dose at which the effect occurred in both male and female rats was from about 75 to 675 times the recommended therapeutic dose for humans. To the best knowledge of the authors, this is the first report of a calcium channel blocker causing constipation in rats.

Animals↗
PubMedDate not supplied

Effect of oxodipine, a novel dihydropyridine calcium channel blocker, in neurogenic hypertensive dogs.

The effects of an acute intravenous injection of oxodipine (5, 20 and 50 micrograms/kg), a new dihydropyridine calcium channel blocker, on blood pressure and heart rate were investigated in arterial neurogenic hypertension elicited in anesthetized dogs by acute sinoaortic denervation. This model is associated with disruption of baroreflex pathways and heart denervation, allowing a direct investigation of the effects of the drug on heart rate and blood vessels. The low dose (5 micrograms/kg) of oxodipine remained ineffective, whereas doses of 20 and 50 micrograms/kg of oxodipine elicited a decrease in blood pressure with no change in heart rate. These results suggest that, in contrast to other first generation dihydropyridines, oxodipine exerts a relatively specific action on blood vessels without significant intrinsic negative chronotropic properties in anesthetized sinoaortic-denervated dogs.

Anesthesia↗