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At least 19 recordsLinked to original sources
PubMed1980

Pharmacokinetic comparison of etilefrine to its prodrug, the stearic acid ester of etilefrine.

The relative bioavailability of a prodrug of etilefrine, its stearic acid ester, was determined by means of plasma levels and renal excretion. The comparison of the plasma levels and renal excretion was carried out in a cross-over design in six subjects. 3H-etilefrine (20 mg) and 3H-2-etylamino-1-(3-stearoylphenyl)ethanol hydrochloride (44.42 mg) were administered orally in equimolecular amounts. The stearic acid ester of etilefrine does not appear in the blood; the ester is split even during absorption. The relative bioavailability of the stearic acid ester of etilefrine, which was determined from the comparison of the areas under the plasma level and the renal excretion, amounts to 51% related to etilefrine. The investigation of the renal excretory products after administration of etilefrine and its prodrug showed the same metabolic pattern. The sulfuric acid ester of etilefrine is the main metabolite. In addition to etilefrine, two basic metabolites are excreted. According to mass- and NMR-spectrometric findings, these two metabolites are two isomeric tetrahydroisoquinolines which formally developed by condensation of etilefrine with formaldehyde. These tetrahydroisoquinolines are excreted free and conjugated with sulfuric acid.

Adult↗
PubMed1985

Comparison of the oral effectiveness of etilefrine pivalate and etilefrine in a long-term trial in man.

The influence of equimolar oral doses of etilefrine pivalate (K 30 052, Ep) and etilefrine on blood pressure of patients suffering from orthostatic dysregulation was compared. Both drugs augmented the systolic blood pressure in both, the upright and horizontal body posture. Diastolic blood pressure was not influenced. The resulting increase in blood pressure amplitude points to an augmentation of cardiac stroke volume. Ep in equimolar doses was nearly twice as active as etilefrine. This result is in line with the hypothesis that acylation of etilefrine with pivalinic acid inhibits the first-pass inactivation nearly completely.

Aged↗
PubMed1985

[Greater oral activity of etilefrine pivalate compared to etilefrine in the cat and dog].

Etilefrine pivalate (K 30 052, Ep) and etilefrine (E) were compared in regard to their effects on the circulation of cats and dogs and in regard to their effects on isolated organs (papillary muscles, atria, vena cava caudalis) of guinea pigs and rabbits. The effects of Ep and E were qualitatively equal. Ep was less effective than E on isolated organs and after intravenous injection, it was however more effective after oral or intraduodenal application. This result is in line with the hypothesis that Ep is inactivated during the first-pass to a smaller extent than E and is split after absorption to E and pivalinic acid.

Animals↗
PubMed1992

Pharmacological analysis of positive chronotropic and inotropic responses to etilefrine in isolated dog heart preparations.

Positive chronotropic and inotropic responses to etilefrine (alpha-[(ethylamino)methyl]-m-hydroxybenzyl alcohol), an orally active cardiovascular agent, were investigated in isolated dog right atrial and left ventricular preparations. Intravenous administration of etilefrine to a support dog increased heart rate and mean systemic blood pressure, and increased sinus rate and atrial contractile force in the isolated right atrium perfused with blood from the support dog. Etilefrine injected intra-arterially to isolated atria and ventricles induced dose-dependent positive chronotropic and inotropic effects. Etilefrine was about 100 times less potent than isoproterenol. The effects of etilefrine in isolated atria were significantly inhibited by treatment with atenolol, but were not significantly inhibited by ICI 118,551. The effects of etilefrine were partially inhibited by imipramine. These results indicate that etilefrine is a highly selective beta-1 adrenoceptor agonist and suggest a moderate catecholamine-releasing activity by tyramine-like action in the blood-perfused dog heart.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

A comparison of the effects of salbutamol, etilefrine and dextran during hypotension and low cardiac output states in rabbit.

The effects of salbutamol (25 and 50 micrograms/kg), etilefrine (50 and 200 micrograms/kg) and dextran (8 ml/kg) on cardiovascular function have been studied in the rabbit. The three drugs raised the resting cardiac output (with salbutamol producing delta max 52%, P less than 0.001, n = 5) and right heart filling pressure (RHFP, delta max from dextran 3.5 cmH2O; P less than 0.001, n = 6) and lowered total peripheral resistance (TPR, delta max from salbutamol 46%, P less than 0.001, n = 5). However, TPR rose with the 200 micrograms/kg etilefrine (P less than 0.05, n = 5). Pulse pressure rose with salbutamol (P less than 0.001, n = 6) and etilefrine (P less than 0.05, n = 6). Etilefrine raised resting BP (delta max, P less than 0.001, n = 6); salbutamol lowered resting BP (delta max, P less than 0.001, n = 6) while dextran (n = 6) had little effect on resting BP. The actions of salbutamol are mediated mainly through beta 2-adrenoceptors although the drug also has some minor beta 1-adrenoceptor action. With etilefrine, the increase in cardiac output and the reduction in TPR are mediated through beta-adrenoceptors while the increases in RHFP, blood pressure and TPR are a direct action on the alpha-adrenoceptors. However, during haemorrhage the fall in diastolic pressure produced by salbutamol was considerably reduced while the reduction in mean BP and systolic pressure (which sometimes rose) was abolished. Dextran raised BP during hypotension produced by either sympathectomy or haemorrhage but not during normotension. The reflex recovery in RHFP and the reflex tachycardia were slightly attenuated during lower body negative pressure (LBNP) after salbutamol or dextran. The reflex recovery in blood pressure was complete and the pressure sometimes exceeded the resting level by up to 10 mmHg during LBNP after salbutamol, etilefrine (50 micrograms/kg only) and dextran. The reduced TPR (presumably due to vasodilation) and the increases in cardiac output and RHFP at an adequately maintained blood pressure produced by suitable doses of the three drugs may be useful in the management of circulatory shock and related states.

Albuterol↗
PubMed1978

The effects of agents modifying sympathetic nerve function on the response of the isolated rat tail artery to etilefrine and tyramine.

The effects of etilefrine on the ventral caudal artery of the rat have been examined in the presence of agents modifying sympathetic nerve function. Catecholamine levels were also measured in adjacent segments of artery to those studied pharmacologically and an attempt made to relate vascular response to etilefrine (and tyramine) with catecholamine content. Both guanethidine and reserpine produced significant attenuation of the vascular effects of etilefrine and tyramine. Pre-treatment with a monoamine oxidase inhibitor caused an increase in tissue catecholamine levels but, paradoxically, depressed the vascular response to etilefrine. The significance of some of the findings in terms of an indirect component to etilefrine's action are discussed.

Animals↗
PubMed1990

Effects of dihydroergotamine and etilefrine on experimentally-induced postural hypotension in dogs.

The effects of dihydroergotamine and etilefrine on experimentally-induced postural hypotension were examined. Although dihydroergotamine at 3 and 10 micrograms/kg (i.v.) increased blood pressure (BP), it did not affect cardiac output (CO). However, dihydroergotamine at 10 micrograms/kg reduced the decrease in CO induced by the tilt. Therefore, it is suggested that the increase in BP is induced by the contraction of resistance vessels, and that the inhibition of the decrease in CO due to tilt is induced by the contraction of capacitance vessels. Etilefrine at 0.1 mg/kg (i.v.) increased BP and heart rate (HR), however, it did not attenuate the decrease in BP induced by the tilt. Although it tended to increase CO, it did not attenuate the decrease in CO. It is suggested that the increase in BP is due to the contraction of resistance vessels, and to the increase in cardiac contractile force and HR. In this study, dihydroergotamine and etilefrine did not attenuate the decrease in BP due to tilt, though dihydroergotamine inhibited the decrease in CO due to tilt. As an explanation, it is suggested that dihydroergotamine induces contraction of resistance vessels as well as capacitance vessels, however the effects of the drug on resistance vessels is weak, and that etilefrine has little or no effect on capacitance vessels. In our previous study, midodrine, an alpha-1 agonist, attenuated the decreases in BP and CO due to tilt, and it has been suggested that the inhibition was induced by the contraction of capacitance vessels. Therefore, dihydroergotamine, etilefrine and midodrine show different pahrmacological profiles in experimentally-induced postural hypotension.

Anesthesia↗
PubMed1985

[Bioavailability of etilefrine from Thomasin and Thomasin sustained-release tablets].

In 6 healthy volunteers absorption and elimination of etilefrine were studied in cross-over after intake of 20 mg each of a solution (A) and tablet (B) (Thomasin) or after intake of 25 mg as a sustained-release tablet (C; Thomasin retard). Etilefrine and its sulfoconjugate were measured by the GC technique in plasma and urine. From the data obtained the AUC-(plasma) and CUE-values (urine) were calculated. Peak plasma levels of 10 to 25 (A) and 6 to 13 ng . ml-1 were observed 30 min after intake. The concentrations decreased to the lower detection limit (less than 2 ng . ml-1) 2 h after intake. Plasma peak levels of 5 ng . ml-1 were measured 1-2 h after intake of the sustained-release form (C). The etilefrine plasma level decreased more slightly (C) than after intake of the other formulations (A, B). The etilefrine conjugate reached plasma peak concentrations of 600 ng . ml-1 1 h (A, B) or 2 h (C) after intake. A mean bioavailability of 70 and 58 per cent (Thomasin) or of 78 and 108 per cent (Thomasin retard) was calculated by comparison of the corresponding AUC- and CUE-values of the total etilefrine.

Adult↗
PubMed1975

The physiological disposition of etilefrine in man.

Pharmacokinetic and metabolic studies with 3H-etilefrine were performed to assess the importance of a first-pass effect on the pharmacodynamic action of this sympathomimetic amine. Identical amounts of 3H-activity, ca. 80% of the dose, were excreted in the urine after intravenous or oral administration, which indicates complete enteral absorption of the drug. Comparison of the areas under the plasma curves of unchanged etilefrine after both routes of administration resulted in a bioavailability factor of 0.55, which can be explained by an extensive first-pass effect. The time curve of plasma levels of etilefrine was compatible with an open 2-compartment model characterized by a rather large volume of distribution (Vd, beta) of 160 1, and a predominant half life of 2 hours. The pharmacodynamic action corresponded to the amount of drug in the central compartment. The major pathway of metabolism of etilefrine was conjugation to form the phenolic sulphate, and a very minor proportion of the drug was excreted as the corresponding hydroxymandelic acid. This metabolic pattern seems to confirm our hypothesis that phenylalkylamines with hydroxyl group in the m-position of the benzene ring are predominantly conjugated in contrast to p-hydroxylated compounds which are mainly deaminated.

Administration, Oral↗
PubMed1975

The cardiovascular effects of etilefrine.

Intravenous etilefrine increases the pulse rate, cardiac output, stroke volume, central venous pressure and mean arterial pressure of healthy individuals. Peripheral vascular resistance falls during the infusion of 1-8 mg etilefrine but begins to rise at higher dosage. Marked falls in pulse rate, cardiac output, stroke volume and peripheral bloodflow, accompanied by rises in mean arterial pressure, occur when etilefrine is infused after administration of intravenous propranolol 2,5 mg. These findings indicate that etilefrine has both beta 1 and alpha adrenergic effects in man.

Adult↗
PubMed1980

The effect of etilefrine (Effortil) on regional blood flow during arterial reconstructive surgery.

Etilefrine is a sympathomimetic amine with high affinity for alpha- and beta2-receptors. Following vascular reconstructions in 38 patients the effect of intravenously administered etilefrine on cardiac output, mean systemic blood pressure, blood flow and vascular resistance of the carotid, subclavian, mesenteric, iliac and femoral arteries was studied intraoperatively. Cardiac output and the mean systemic blood pressure were significantly increased. The blood flow was increased in all the arterial beds studied distribution. The peripheral vascular resistance was considerably decreased for the subclavian, iliac and femoral arteries' regions of supply but unchanged or increased for those of the carotid and mesenteric arteries. This discrepancy may be explained by the different effects of etilefrine on the vascular resistance of parenchymatous and of muscular regions, but it is also possible that the effect of etilefrine on the blood flow to the intestines and brain is counteracted by autoregulation.

Adult↗
PubMed1991

Comparison of ephedrine and etilefrine for the treatment of arterial hypotension during spinal anaesthesia in elderly patients.

Thirty ASA II-III patients (greater than 65 years) undergoing hip surgery under bupivacaine spinal anaesthesia, and presenting a 25% reduction in mean arterial pressure (MAP), were included in the study. The patients were randomly allocated to receive, under double-blind conditions, either ephedrine 0.07 mg kg-1 or etilefrine 0.03 mg kg-1 boluses i.v. when MAP decreased by 25% from the preanaesthetic reference value. There were no significant differences (mean +/- s.d.) in the time interval between the sympathomimetics administered (ephedrine 20.2 +/- 17.1 min, etilefrine 16.6 +/- 7.0 min) or the number of sympathomimetics needed (ephedrine 3.8 +/- 1.9, etilefrine 3.6 +/- 2.2). In regard to MAP and diastolic arterial pressure (DAP), ephedrine was slightly more potent in restoring arterial blood pressure compared with etilefrine. The increases in systolic arterial pressure (SAP) and heart rate were similar in both groups. The administration of repeated doses of either sympathomimetic showed the same tendency to increase SAP, DAP, and MAP values as the first dose.

Aged↗
PubMed1986

[Intracavernous injection of etilefrine hydrochloride in iatrogenic priapism].

Intracavernous injection of etilefrine hydrochloride (1 or 2 mg) was performed on four patients with fully erected penis after intracavernous injection of 40 mg of papaverine hydrochloride. One case needed three injections of etilefrine hydrochloride (1 mg), but the erection disappeared in the other three cases within 10 minutes after a single injection of 2 mg of etilefrine hydrochloride. The injection resulted in complete detumescence and relief of the erection in all cases. These observations strongly suggest that the intracavernous injection of etilefrine hydrochloride is effective in treating not only iatrogenic priapism but also priapism due to other etiologies. Also, it might be useful to control erection time after intracavernous injection therapy for impotence.

Adult↗
PubMed1987

The action of relaxin, fenoterol and etilefrine on uterine motility of the rat.

In uterine motility tests in virgin rats, the inhibitory action of the peptide hormone relaxin has been compared with the actions of fenoterol and etilefrine. At molecular levels, relaxin and fenoterol showed similar uterine inhibitory activity. Etilefrine was markedly less effective in inducing uterine relaxation. By pretreatment with propranolol, the inhibitory action of both fenoterol and etilefrine could be prevented but not the tocolytic effect of relaxin. Etilefrine, in higher doses, developed alpha-receptor activity as demonstrated by resumed uterine contractions. The doses required to induce beta 2- and alpha-activities differed by a factor of approximately 4,000.

Animals↗
PubMed1989

Etilefrine and amezinium reduce uterine blood flow of pregnant guinea pigs.

Etilefrine and Amezinium are used during pregnancy to prevent hypotension and fetal growth retardation. The effect of these drugs on uterine blood flow (UBF), uterine vascular resistance (UVR) and fetal growth are, however, unknown. 31 guinea pigs were injected daily with Etilefrine (3 X 0.14 mg/kg) and Amezinium (0.14 mg/kg) from day 30 to day 60. Uterine blood flow was measured with radioactive-labeled microspheres. Uterine vascular resistance was calculated from arterial blood pressure and uterine blood flow. 10 guinea pigs treated with 0.9% sodium chloride served as controls. As a response to Etilefrine and Amezinium, UBF fell by 68 and 48%, respectively, accompanied by an increase in UVR. The fetal weight decreased only slightly. It is concluded that long-term application of anti-hypotensive drugs may be hazardous to uterine blood flow and fetal growth.

Animals↗
PubMed1979

Vascular effects of etilefrine. Further studies to substantiate the predominant indirect sympathomimetic action of this agent.

The suggested use of etilefrine in the treatment of patients with orthostatic hypotension is based on the premise that it has an action similar to that of noradrenaline (Miller, Wiener and Bloomfield, 1973). However, earlier work from this laboratory (Frost, Frewin and Gerke, 1977; Frost, Frewin, Gerke and Downey, 1978; Frost, Halloran, Frewin, Gerke and Downey, 1978) on blood vessels in the rat tail has suggested that the drug acts predominantly as an indirect sympathomimetic agent. The present study examined the action of etilefrine on the central artery of the rabbit ear. This vessel is known to have a rich sympathetic innervation (de la Lande, Frewin and Waterson, 1967) and has the added advantage that it can be surgically denervated. It therefore became possible to examine the effects of etilefrine on both normal and denervated arteries and to quantitate the extent to which the drug relied on the symphathetic nerves for its vasoconstrictor effects.

Animals↗
PubMed1977

The effects of etilefrine on blood vessels in the rat tail.

Etilefrine was found to constrict blood vessels in the rat tail through a mechanism which was partly dependent on the sympathetic nerves present in these vessels. The response to the drug was enhanced by pretreagment with noradrenaline and cocaine, and totally abolished by the alpha-receptor antagonist phentolamine. When compared with several other sympathomimetic agents which were tested on the vessel, etilefrine appeared to have a low order of vasoconstrictor activity. These findings would seem to have considerable relevance to the clinical situation where an attempt has been made to use etilefrine in the treatment of patients with orthostatic hypotension.

Animals↗