InChI=1S/C11H11N3O/c1-15-11-7-9(12)8-13-14(11)10-5-3-2-4-6-10/h2-8,12H,1H3/p+1 |
VXROHTDSRBRJLN-UHFFFAOYSA-O |
O(C=1[N+](=NC=C(C1)N)C2=CC=CC=C2)C |
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Bronsted base
A molecular entity capable of accepting a hydron from a donor (Bronsted acid).
(via organic amino compound )
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EC 1.4.3.4 (monoamine oxidase) inhibitor
An EC 1.4.3.* (oxidoreductase acting on donor CH-NH2 group, oxygen as acceptor) inhibitor that interferes with the action of monoamine oxidase (EC 1.4.3.4).
sympathomimetic agent
A drug that mimics the effects of stimulating postganglionic adrenergic sympathetic nerves. Included in this class are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters.
adrenergic uptake inhibitor
Adrenergic uptake inhibitors are drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin.
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antihypotensive agent
A cardiovascular drug that tends to raise reduced blood pressure.
sympathomimetic agent
A drug that mimics the effects of stimulating postganglionic adrenergic sympathetic nerves. Included in this class are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters.
adrenergic uptake inhibitor
Adrenergic uptake inhibitors are drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin.
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View more via ChEBI Ontology
4-amino-6-methoxy-1-phenylpyridazin-1-ium
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4-amino-6-methoxy-1-phenyl-pyridazinium
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ChemIDplus
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amezinium(1+)
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ChEBI
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4141517
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Beilstein Registry Number
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Beilstein
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41658-78-0
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CAS Registry Number
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ChemIDplus
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Ichiyanagi O, Sasagawa I, Suzuki Y, Matsuki S, Itoh K, Miura M, Tomita Y (2003) Successful treatment of retrograde ejaculation with amezinium. Archives of andrology 49, 215-217 [PubMed:12746100] [show Abstract] The effect of amezinium, a new type of antihypotensive agent, on retrograde ejaculation was evaluated in 3 patients with retrograde ejaculation. The patients received 10 mg amezinium orally once a day. All patients achieved antegrade ejaculation. Semen analyses revealed 6-50 x 10(6)/mL (mean 28.7 x 10(6)/mL) sperm with a motility of 20-50% (mean 36.7%). The wives of 2 patients became pregnant within 6 months of the initial treatment. None of the patients had any side effects. It would appear that amezinium is a useful treatment for retrograde ejaculation. | Kokot Z, Prawdzik I (2001) Determination of amezinium in plasma by RP HPLC and its application to bioequivalence studies. Acta poloniae pharmaceutica 58, 315-318 [PubMed:11876436] [show Abstract] A modified method is described for the determination of 4-amino-6-methoxy-l-phenylpyridazinium methyl sulfate (amezinium metisulfate) in plasma and in the dosage form. The method involves a sample preparation using SPE and liquid-liquid extraction and subsequent determination by high performance liquid chromatography. Retention time for amezinium was 3.2 min and there was no interference from plasma or amezinium metabolites. The method was applied for the drug determination during comparative studies of two different tablet formulation of amezinium. | Shimizu I, Ishii D, Kawashima K, Oka M, Hosoki K (2001) Pharmacological effect of amezinium on urethra and bladder of rabbits. International urogynecology journal and pelvic floor dysfunction 12, 170-177 [PubMed:11451005] [show Abstract] The pharmacological effect of amezinium on the urethra and bladder of rabbits was investigated. Amezinium produced concentration-dependent contractions in isolated urethral strips. The maximum response was approximately 30% of that caused by norepinephrine (NE). The concentration-response curve of NE was shifted to the left by amezinium. Moreover, amezinium enhanced the relaxative effect of NE on carbachol-induced contractions in isolated bladder strips. In anesthetized rabbits, amezinium significantly increased the intraurethral pressure (IUP) but produced only slight increases in mean blood pressure (MBP). Pre-treatment with amezinium ehhanced NE-induced increases in IUP index and MBP. The enhancing effect on the IUP index lasted much longer than that on MBP. In a stress incontinence model amezinium significantly inhibited the incontinence after an i.v. infusion of a low dose of NE. This effect was antagonized by pre-treatment with prazosin. These results suggest that amezinium may produce an excellent effect for stress incontinence, especially mixed, without severe adverse events such as sudden hypertension. | Miura H, Tsuchiya K, Kubodera T, Shimamura H, Matsuoka T (2001) [An autopsy case of pure autonomic failure with pathological features of Parkinson's disease]. Rinsho shinkeigaku = Clinical neurology 41, 40-44 [PubMed:11433766] [show Abstract] Pure autonomic failure (PAF) is an uncommon disorder, characterized by autonomic failure without other neurological deficits. We report here an autopsy case of pure autonomic failure with pathological features of Parkinson's disease. At age 79, the patient developed slowly progressive severe orthostatic hypotension, followed by decreased sweating and constipation. On admission, his blood pressure dropped after standing (from 133/97 to 71/22 mmHg) without tachycardia. Neurological examination revealed neither parkinsonism, nor cerebellar symptoms. Supine plasma norepinephrine levels were low and intravenous norepinephrine administration showed denervation hypersensitivity. He was diagnosed as having PAF and treated by amezinium, midodrine, L-threodops, and fludrocortisone with elastic stockings but without any effects. He died of pneumonia about 2 years after the onset of the disease. Postmortem study revealed Lewy bodies in the nucleus basalis of Meynert, substantia nigra. Edinger-Westphal nucleus, locus ceruleus, and dorsal vagal nucleus. Neuronal loss was found in above-mentioned sites, except for Edinger-Westphal nucleus and intermediolateral nucleus. This is a rare and important report on a patient with PAF who satisfied the strict clinical criteria on PAF reported in 1996, and showed neuropathological findings, consistent with Parkinson's disease. | Kurihara J, Takata Y, Suzuki S, Okubo Y, Kato H (2000) Effect of midodrine on chlorpromazine-induced orthostatic hypotension in rabbits: comparison with amezinium, etilefrine and droxidopa. Biological & pharmaceutical bulletin 23, 1445-1449 [PubMed:11145175] [show Abstract] Orthostatic hypotension was produced in urethane-anesthetized rabbit by a combination of chlorpromazine (0.1 mg/kg, i.v.) and 45 degrees head-up tilt. The effect of midodrine (1 and 3 mg/kg, i.d.) was investigated in comparison with amezinium (10 and 30 mg/kg, i.d.), etilefrine (10 and 30 mg/kg, i.d.) and droxidopa (30 and 100 mg/kg, i.d.). The higher doses of each drug significantly mitigated the chlorpromazine-induced orthostatic hypotension, while none of the lower doses caused a significant effect. The effect of midodrine developed most rapidly; a significant effect was observed 25 min after administration. The order of onset time was midodrine < etilefrine < amezinium < droxidopa. The effect of droxidopa was significant only at 130 to 160 min after administration. The amplitude of effect was in the following order; midodrine = droxidopa > or = etilefrine > amezinium. Midodrine (3 mg/kg, i.d.) mitigated orthostatic hypotension induced by prazosin (0.1 mg/kg, i.v.), but not by pentolinium (0.6 mg/kg, i.v.). It is suggested that midodrine competes with chlorpromazine at alpha1-adrenoceptors and subsequently recovers reflex vasoconstriction. Midodrine may be useful to protect patients with impaired baroreflex activity from accidental orthostatic hypotension during treatment with neuroleptics. | Ishigooka M, Hashimoto T, Suzuki Y, Aoyama N, Sasagawa I, Nakada T (1999) In vitro effect of amezinium on the rabbit urinary bladder: muscle strip and whole bladder evaluation. International urology and nephrology 31, 181-188 [PubMed:10481962] [show Abstract] Dose-response studies for norepinephrine and amezinium were obtained for isolated muscle strips and in vitro whole bladder preparations to investigate the effect of amezinium on the bladder. Specimens (strips from the bladder base and body, and the whole bladder) were obtained from mature female rabbits. By the muscle strip study, amezinium showed a weak contractile effect (up to 40% of spontaneous contraction) on strips from the bladder base. Muscle strips from the bladder body presented no response to amezinium. In the whole bladder preparation, administration of norepinephrine showed an increase in intravesical pressure in 4 out of 7 rabbits, whereas administration of amezinium had negligible effect on intravesical pressure. Administration of amezinium showed no influence on strips from the bladder body and the whole bladder preparation. Direct contractile response in muscle strips from the bladder base by amezinium appeared to be a favourable effect considering urinary storage. | Ishigooka M, Hashimoto T, Suzuki Y, Ichiyanagi O, Sasagawa I, Nakada T (1996) Direct effect of amezinium on rabbit urethra: effect of estrogen and progesterone treatment. International urogynecology journal and pelvic floor dysfunction 7, 325-330 [PubMed:9203481] [show Abstract] The effect of amezinium, a new anti-hypotensive agent, and hormonal treatment on the female rabbit urethra was investigated. Cumulative dose responses were obtained for amezinium and norepinephrine on strips of muscle from the urethras of ovariectomized female rabbits by means of the tissue-bath system. Amezinium enhanced the response to electrical field stimulation and showed a direct contractile response on the urethra. These responses were only about 20% of the maximum norepinephrine response. The contractile response to amezinium was completely blocked by prazosin. When rabbits were pretreated with estrogen, with or without progesterone, for 4 weeks, the response to amezinium increased to 40% of the maximum norepinephrine response. Although amezinium enhances muscle contractile responses to electrical stimulation, this effect is strong when amezinium is used alone; concurrent estrogen treatment improves the effects of amezinium. | Bryan-Lluka LJ, Seers H, Sharpe I (1996) Amezinium and debrisoquine are substrates of uptake1 and potent inhibitors of monoamine oxidase in perfused lungs of rats. Naunyn-Schmiedeberg's archives of pharmacology 353, 536-544 [PubMed:8740147] [show Abstract] Previous studies have resulted in the classification of amezinium as a selective inhibitor of neuronal monoamine oxidase (MAO), because it is a much more potent MAO inhibitor in intact tissues, in which it is accumulated in noradrenergic neurones by uptake1, than in tissue homogenates. In the present study, the effects of amezinium on the deamination of noradrenaline were investigated in intact lungs of rats, since the pulmonary endothelial cells are a site where the catecholamine transporter is non-neuronal uptake1. In addition, another drug that is both a substrate of uptake1 and a MAO inhibitor, debrisoquine, was investigated in the study. The first aim of the study was to show whether amezinium and debrisoquine are substrates of uptake1 in rat lungs. After loading of isolated perfused lungs with 3H-noradrenaline (MAO and catechol-O-methyltransferase (COMT) inhibited), the efflux of 3H-noradrenaline was measured for 30 min. When 1 mumol/l amezinium or 15 mumol/l debrisoquine was added for the last 15 min of efflux, there was a rapid and marked increase in the fractional rate of loss of 3H-noradrenaline, which was reduced by about 70% when 1 mumol/l desipramine was present throughout the efflux period. These results showed that both drugs were substrates for uptake1 in rat lungs. In lungs perfused with 1 nmol/l 3H-noradrenaline (COMT inhibited), 10, 30 and 300 nmol/l amezinium caused 58%, 76% and 74% inhibition of noradrenaline deamination, respectively, and 30, 300 and 3000 nmol/l debrisoquine caused 56%, 89% and 96% inhibition of noradrenaline deamination, respectively. When MAO-B was also inhibited, 10 nmol/l amezinium caused 84% inhibition of the deamination of noradrenaline by MAO-A in the lungs. In contrast, in hearts perfused with 10 nmol/l 3H-noradrenaline under conditions where the amine was accumulated by uptake2 (COMT, uptake1 and vesicular transport inhibited), 10 nmol/l amezinium had no effect and 300 nmol/l amezinium caused only 36% inhibition of deamination of noradrenaline. The results when considered with previous reports in the literature show that amezinium is about 1000 times more potent and debrisoquine is about 20 times more potent for MAO inhibition in rat lungs than in tissue homogenates, and the reason for their high potencies in the intact lungs is transport and accumulation of the drugs in the pulmonary endothelial cells by uptake1. Amezinium is much less potent as a MAO inhibitor in cells with the uptake2 transporter, such as the myocardial cells of the heart. The results also confirmed previous reports that amezinium is highly selective for MAO-A. | Hohmann M, Künzel W (1989) Etilefrine and amezinium reduce uterine blood flow of pregnant guinea pigs. European journal of obstetrics, gynecology, and reproductive biology 30, 173-181 [PubMed:2564830] [show Abstract] 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. | Müller H, Brähler A, Börner U, Boldt J, Stoyanov M, Hempelmann G (1985) [Hemodynamic effects following bolus administration of different vasopressive agents for blood pressure stabilization during peridural anesthesia]. Regional-Anaesthesie 8, 43-49 [PubMed:2863856] [show Abstract] Vasopressors are often used to counteract hypotension induced by sympathetic blockade during epidural or spinal anaesthesia. This study contains data of invasive haemodynamic investigations following single-shot applications of different vasoconstrictor agents (Akrinor, etilefrine, ephedrin, norfenefrin, amezinium) during a combination of epidural block and controlled ventilation with oxygen and nitrous oxide. In a preceding dose finding study equipotent dosage of the substances used was confirmed. Usually bolus application of these vasopressors causes only a short-lasting circulatory stimulation, which does not cover the whole period of sympathetic blockade (exception: amezinium). Even small doses of drugs acting only upon alpha-receptors, may cause unwanted peripheral vasoconstriction and decrease of the already lowered cardiac output (example: norfenefrine). The rise of blood pressure after betamimetics may be delayed by an initial vascular beta 2 stimulation (example: etilefrine). In other sympathetic stimulants venoconstriction and therefore improvement of cardiac output by increase of preload takes place after an interval of some minutes to cardiac stimulation (example: ephedrin, Akrinor). Though the use of vasopressor agents during central blockade cannot be recommended in general, substances with alpha- as well as beta-stimulation should be preferred, if necessary. When using substances with short duration of action continuous infusion has to be taken into consideration. | Lenzen S, Nahrstedt H, Panten U (1983) Monoamine oxidase in pancreatic islets, exocrine pancreas, and liver from rats. Characterization with clorgyline, deprenyl, pargyline, tranylcypromine, and amezinium. Naunyn-Schmiedeberg's archives of pharmacology 324, 190-195 [PubMed:6419132] [show Abstract] Monoamine oxidase (MAO) was characterized in tissue homogenates from pancreatic islets, exocrine pancreas, and liver from rats. Phenylethylamine was preferentially deaminated by pancreatic islet MAO while 5-hydroxytryptamine was preferentially deaminated by MAO from exocrine pancreas, and tyramine was a good substrate for both tissues. All three substrates were well deaminated by liver tissue. Clorgyline, a selective inhibitor of MAO-A, preferentially inhibited deamination of 5-hydroxytryptamine by all three tissue homogenates, while deprenyl, a selective inhibitor of MAO-B, preferentially inhibited deamination of phenylethylamine. In the case of pargyline, a less selective MAO-B inhibitor, the preference in favour of phenylethylamine was less pronounced. According to these results, MAO in pancreatic islets can be classified as predominantly type B enzyme species and MAO in exocrine pancreas as predominantly type A enzyme species while both types of the enzyme are present in the liver. Using the same three MAO substrates and compared with the effects of the selective enzyme inhibitors, clorgyline and deprenyl, tranylcypromine can be classified as a potent nonselective inhibitor of MAO in homogenates of all three tissues investigated with a slight preference in favour of the inhibition of the B-form of the enzyme, while in contrast amezinium can be classified as a weak nonselective inhibitor of MAO with a slight preference in favour of the inhibition of the A-form of the enzyme. All MAO inhibitors tested also inhibited insulin secretion by isolated incubated rat pancreatic islets, however only at IC50 which were two to three decimal powers higher than those necessary for the inhibition of the MAO activity, thus indicating that inhibition of MAO activity and inhibition of insulin secretion are apparently not closely related. | Traut M, Morgenthaler H, Brode E (1981) Determination of amezinium in body fluids. Arzneimittel-Forschung 31, 1589-1593 [PubMed:7030355] [show Abstract] Possible approaches to the determination in body fluids of 4-amino-6-methoxy-1-phenyl-pyridazinium methyl sulfate (ameziniummetilsulfate, LU 1631, Regulton), in this study briefly called amezinium, are investigated and the methods developed on the basis of results obtained in pilot experiments described. These methods, which are primarily based on radioactive tracer techniques, allow both labelled and unlabelled amezinium to be determined in urine, bile, blood, and plasma in concentrations down to about 2 n/ml. Relative standard deviations of 0.5%-9% and 96-102% accuracy are obtained. Advantages and disadvantages of individual methods for various types of samples are discussed. | (1981) Amezinium (LU 1631, Regulton). Arzneimittel-Forschung 31, 1527-1671 [PubMed:7197966] | Traut M, Brode E, Neumann B, Kummer H (1981) Pharmacokinetics of amezinium in rat and dog. Arzneimittel-Forschung 31, 1594-1604 [PubMed:7197974] [show Abstract] Using 14C-labelled 4-amino-6-methoxy-1-phenyl-pyridazinium methyl sulfate (ameziniummetilsulfate, LU 1631, Regulton), briefly called amezinium, the time course of plasma level in the rat and of blood level and renal excretion rate in the dog has been followed. The distribution of radioactivity in the organism was investigated by autoradiography of whole-animal sections and by quantitative radioactivity determinations in rat tissue as well as by in vitro experiments. From the results we draw the following conclusions: 1. In the two species investigated here, amezinium is almost completely absorbed after enteral administration. In the rat the absorption proceeds with a half-life of 11 min, after a lag phase of 6 min. In the dog, the lag phase is 30-40 min, after which the compound is absorbed with a half-life of 30 min or less. The small intestine appears to be the site of absorption. 2. Amezinium has a high affinity for tissues. Its transport through the cell membrane, in the case of sympathetic neurons and probably also in the case of other chromaffin cells, is mediated by the noradrenaline carrier; in other tissues, for example the liver, a different active transport mechanism, as yet not elucidated, is operating. The placenta and blood-brain barrier are passed only slightly, if at all. In rat blood amezinium distributes between erythrocytes and plasma with a ratio of 2.7:1; the proportion bound to plasma proteins is about 20%. 3. In the rat amezinium is eliminated from the circulation to the extent of about 3/4 by biotransformation; on enteral administration, about 80% is trapped by first-pass metabolism. In the dog biotransformation accounting for about 40% of the elimination is relatively unimportant; the first-pass metabolism is virtually negligible. 4. Amezinium is eliminated by rats about equally with urine and bile, whilst in the dog the predominant proportion is excreted renally. From plasma level curves the terminal half-life t 1/2 (beta) in the rat was found to be 17 h and 21 h after i.v. and p.o. administration, respectively; blood level data and urinary excretion data in the case of the dog gave 5 1/2 (beta) values between 11 h and 20 h. 5. Renal clearance of amezinium in the dog is not constant: initially it is several times greater than the glomerular filtration rate (GFR) decreasing subsequently to about the same magnitude or even below the GFR. | Traut M, Brode E (1981) Pharmacokinetics of amezinium in man. Arzneimittel-Forschung 31, 1605-1615 [PubMed:7197975] [show Abstract] Pharmacokinetics of 4-amino-6-methoxy-1-phenyl-pyridazinium methyl sulfate (ameziniummetilsulfate, LU 1631, Regulton), in the following briefly called amezinium, was studied in two groups of subjects. The substance was administered i.v. (1 mg and 10 mg) and p.o. (40 mg and 50 mg), resp. In all cases the time course of renal excretion rate was followed; in two studies blood levels were determined additionally. Together with findings from animal experiments the results are used to describe the pharmacokinetic behaviour of amezinium in man at the present state of knowledge: 1. Absorption of amezinium administered p.o. is preceded by a lag phase which depends on the dissolution time of the tablets used. After the lag phase absorption takes place with a half-life of less than 30 min. 2. Absolute bioavailability of the batches used is estimated to be about 50% and 67% resp. 3. Amezinium is distributed rapidly into the tissues. The first distribution phase detectable has a half-life of less than 10 min. Steady state volumes of distribution are calculated to be between 2 and 3 l/kg. 4. Amezinium and its metabolites are excreted predominantly by the kidneys; extrarenal elimination amounts to about 30%. Terminal half-life was determined from blood levels and excretion data after i.v. as well as p.o. administration to be between 9 and 17 h. 5. Renal clearance of amezinium is not constant. Initially it exceeds the glomerular filtration rate (GFR) by a factor of 4, later it decreases to values similar to the GFR. Comparison of the time courses of the renal excretion on the one hand and of the blood level on the other indicates that renal handling of amezinium may be influenced by its own pharmacological action. This anomalous clearance behaviour of amezinium is considered to be favourable with respect to drug safety. | Traut M, Kummer H, Brode E (1981) The fate of amezinium in humans and animals. Arzneimittel-Forschung 31, 1616-1622 [PubMed:7197976] [show Abstract] The metabolism of 14C-labelled 4-amino-6-methoxy-1-phenyl-pyridazinium methyl sulfate (ameziniummetilsulfate, LU 1631, Regulton), in the following briefly called amezinium, was studied in 6 animal species (dog, cat, rabbit, guinea-pig, rat, and mouse) and in humans. Two-dimensional thin-layer radiochromatography revealed qualitative and quantitative differences between species. In man, dog, cat, guinea-pig, and mouse unchanged amezinium is the principal excretion product, accounting for 56-89% of the radioactivity in the urine whilst metabolites predominate in the rabbit and particularly in the rat. Since besides unchanged amezinium (I) no radioactive substance from the urine is adsorbed on cation exchanger, the first step of biotransformation is assumed to be the formation of uncharged, pharmacologically inactive 5-amino-2-phenyl-3(2H)-pyridazinone (II). The metabolites excreted by man and dog have largely been identified; apart from small quantities of II, hydroxylated pyridazinones and/or their sulfuric acid conjugates were isolated. The formation of the metabolites is discussed. | Wilsmann K, Neugebauer G, Kessel R, Lang E (1981) Haemodynamic effects of amezinium in man. Arzneimittel-Forschung 31, 1638-1646 [PubMed:7197978] [show Abstract] After single i.v. (5 and 10 mg) and p.o. (10, 20 and 40 mg) administrations, 4-amino-6-methyoxy-1-phenyl-pyridazinium methyl sulfate (ameziniummetilsulfate, LU 1631, Regulton), in the following briefly called amezinium, a new antihypotensive agent, was studied by non-invasive methods for its cardiovascular action in comparison with norfenefrine (10 mg i.m. and 40 mg p.o.) and dihydroergotamine (1 mg i.m. and 4 mg p.o.) in a group of 33 volunteers. The action pattern of 10 mg amezinium i.v. consisted of a significant rise in arterial blood pressure (systolic 23%, diastolic 14%) with an increase in pulse pressure (38%) and a reflex fall in heart rate (9%). The total peripheral resistance was increased by 29%, with a moderate reduction of cardiac output (5%; n.s.) and an increase of the stroke volume (6%; n.s.). A clear positive inotropic effect was discernible by the significant reduction of heart rate, corrected preejection period (delta PEP; 13 ms), left ventricular ejection time (delta LVET; 8 ms; n.s.) and a decrease of the ratio PEP/LVET (-0.028). This pattern of action points to stimulation of vascular alpha- as well as cardiac beta 1-adrenoceptors and is in accordance with the findings from animal experiments as amezinium acts via endogenous noradrenaline. The reference substance norfenefrine exhibited purely alpha-sympathomimetic action, whereas dihydroergotamine presumably exerted venoconstrictive and central sympatholytic effects. The effects of amezinium after p.o. administration on the circulation were similar to those after i.v. administration, whereas the reference substances did not reveal any definite pharmacodynamic action when given p.o. Single administrations of the various p.o. doses of amezinium gave rise to a dose-dependent increase of the systolic blood pressure, persisting over the 180 min of the investigation period. From the dose-response relationships after parenteral and oral administration a relative enteral efficacy of 50-80% was established, which corresponds well with bioavailability data. The results show amezinium to have potent, long-lasting blood pressure increasing and positive inotropic actions in man after oral as well as parenteral administration. |
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