Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Aminorex”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1994

Evaluation of the abuse liability of aminorex.

Aminorex is a cyclic phenylisopropylamine that has been marketed as an anorectic. Despite obvious pharmacological similarities to the amphetamines, little is known about its liability for abuse. In the present study, one group of rhesus monkeys (n = 3) was prepared with intravenous catheters and allowed to self-administer either methohexital or saline in daily experimental sessions. When methohexital and saline self-administration were stable and clearly different, various doses of aminorex (0.001-0.1 mg/kg/injection) were made available for self-administration. Aminorex maintained self-administration above that maintained by saline and slightly lower than that maintained by methohexital in all monkeys. The discriminative stimulus effects of aminorex were evaluated in rhesus monkeys trained to discriminate d-amphetamine (n = 3) or pentobarbital (n = 4) from saline. Aminorex substituted completely for d-amphetamine as a discriminative stimulus but engendered little or no pentobarbital-appropriate responding. Aminorex stimulated locomotor activity in mice and exacerbated the withdrawal syndrome in rats that were dependent upon pentobarbital. These findings indicate that aminorex is a psychomotor stimulant that would be predicted to have significant d-amphetamine-like abuse liability in humans.

Aminorex↗
PubMed1992

Aminorex produces stimulus effects similar to amphetamine and unlike those of fenfluramine.

A 4-methyl derivative of aminorex has recently appeared on the clandestine market as a designer drug. In the present study, the stimulus effects of aminorex itself were evaluated in rats trained to discriminate either 0.75 mg/kg S(+)-amphetamine or 1.5 mg/kg fenfluramine from saline. The amphetamine stimulus (ED50 = 0.14 mg/kg) generalized to aminorex (ED50 = 0.23 mg/kg), which was found to be slightly less potent than (+)-amphetamine. Fenfluramine stimulus generalization did not occur to aminorex. Thus, the stimulus effects of aminorex are qualitatively similar to those of amphetamine and unlike those of fenfluramine.

Aminorex↗
PubMed1998

Aminorex, dexfenfluramine, and primary pulmonary hypertension.

BACKGROUND: In the late 1960s, an epidemic of primary pulmonary hypertension (PPH) occurred in Europe shortly after the introduction of aminorex fumarate, a potent anorexigen. A recently published case-control study from Europe reported that use of other anorexigens (the most prevalent of which was dexfenfluramine) was also associated with an increased risk of PPH. This led to warnings of a repeat epidemic, especially after the introduction of dexfenfluramine on the North American market. OBJECTIVE: To compare the epidemiologic associations of PPH with aminorex and dexfenfluramine, both with respect to strength of association (estimate of relative risk) and public health impact (etiologic fraction) and thus to assess the potential for a new epidemic of PPH. METHODS: We constructed a "synthetic" case-control study for aminorex based on reported case series from Berne and Basel, Switzerland, and a random population sample from Hanover, Germany, and compared the results with those recently reported for dexfenfluramine. Control rates of exposure were used to estimate population exposure prevalences and, hence, etiologic fractions. RESULTS: The estimated odds ratio (and 95% confidence interval) for the association between PPH and any exposure to aminorex was 97.8 (78.9-121.3), with a corresponding etiologic fraction of 77%. The corresponding figures for dexfenfluramine were 3.7 (1.9-7.2) and 17%, respectively. CONCLUSION: The strong association between aminorex and PPH probably led to a 5-fold increase in PPH incidence, and thus a very noticeable epidemic. The association with dexfenfluramine would result in an increase in incidence of only 20%. Based on the available evidence, a repeat PPH epidemic seems unlikely.

Adult↗
PubMed1985

[Chronic pulmonary hypertension of vascular origin, plexogenic pulmonary arteriopathy and the appetite depressant aminorex: addenda to an epidemic].

An epidemic of chronic pulmonary hypertension occurred in Austria, the Federal Republic of Germany, and Switzerland, starting in 1967, peaking in 1968/69, and disappearing after 1972. The mechanism leading to pulmonary hypertension was precapillary vascular obstruction due to plexogenic pulmonary arteriopathy. There was a close geographic and temporal relationship between the epidemic and the marketing and intake of the appetite-depressing drug aminorex fumarate (Menocil). The epidemic was limited to the three above countries where aminorex had been on sale. In the individual patient the symptoms, usually dyspnea, angina pectoris and syncope on exertion, used to follow the beginning of the drug in-take after one year. A similar phase shift could be observed between marketing of the anoretic and the incidence of patients with chronic pulmonary hypertension of vascular origin. The new disease is compared with known forms of pulmonary vascular obstruction. It cannot be distinguished from classical primary pulmonary hypertension or from recurrent silent pulmonary thromboembolism on either clinical or functional grounds; it has plexogenic pulmonary arteriography in common with the former. The prognosis, however, is different: survival is considerably longer in patients with aminorex-associated pulmonary hypertension, and a marked decrease in the pulmonary vascular obstruction after 10 years is no exception. Considering the closeness of the various associations between the event (i.e. the epidemic) and its suspected cause (the anoretic aminorex) from the viewpoint of epidemiological, pharmacological, morphological and prognostic findings and considerations, there is little doubt that aminorex, besides other partly known and partly unknown factors, can in fact favour or cause the development of plexogenic pulmonary arteriography and pulmonary hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Pulmonary hypertension, "plexogenic pulmonary arteriopathy" and the appetite depressant drug aminorex: post or propter?

An epidemic of chronic pulmonary hypertension of vascular origin (CPHVO) has occurred in Austria, the Federal Republic of Germany, and Switzerland. The epidemic started in 1967 and reached its peak in 1968 and 1969. Since 1972, the prevalence of patients with CPHVO among individuals investigated by cardiac catheterization is again as low as in the pre-epidemic years. In Bern the prevalence of CPHVO during the peak of the epidemic was 20 times higher than during the 12-year period preceding the epidemic. The clinical, physical, electrocardiographic, radiologic, haemodynamic and respiratory findings of the patients observed in Bern (n = 102) are summarized. There has been a mortality between 12 and 20% at the time of the epidemic. Most patients observed for the first time during the epidemic have remained severely disabled over the years. A minute fraction seems to have recovered. There is a close geographic as well as temporal relation of the epidemic to the marketing and intake of the appetite depressing drug aminorex fumarate (Menocil). Acute administration of aminorex leads to a transient rise of the pulmonary artery pressure and vascular resistance in a number of animal species. It has not been possible to produce sustained precapillary pulmonary hypertension and chronic cor pulmonale vasculare under the conditions of chronic administration of the drug in the species tested. Morphologic examination of lung biopsy and autopsy material of patients who have died from CPHVO after the intake of aminorex reveals the presence of "plexogenic pulmonary arteriopathy". The vascular lesions are identical with those observed in pulmonary hypertension due to large congenital left-to-right shunts. In balancing the pros and cons, it appears that the arguments in favour of a cause-effect relationship between aminorex and pulmonary hypertension, which are derived from epidemiological evidence, outweigh the results of "negative" animal experiments. A "propter" in the title of this paper, therefore, seems to be more appropriate than a post".

Adolescent↗
PubMed1975

[Two-year peroral administration of aminorex in the dog. 2].

In an attempt to develop an experimental model of pulmonary hypertension, five mongrel dogs were treated with 1 mg/kg p. o. and five with 1.5 mg/kg p. o. of Aminorex base five days a week for two years. A control group was given empty capsules by months. The following effects of treatment with Aminorex were noted: 1. Anorexia and central stimulation, 2. Natriuresis, 3. an increase in respiration rate, heart rate and body temperature, 4. a tendency towards usually compensated metabolic acidosis, 5. an increase in pulmonary arterial pressure, total pulmonary resistance and right ventricular work, and, in the group given the higher dose, a slight increase in mean aortic pressure and peripheral resistance. 6. Only slight histopathological changes were detectable, e.g.: perivascular oedema; increase in the number of muscle arteries, occasionally with hypertrophy of the tunica media and slight, focal fibro-elastoid thickening of the intima in some elastic arteries. These changes were present in about 60% of the treated dogs. Only one dog that died after 91 weeks' treatment also showed moderate, focal phlebosclerosis of large pulmonary veins and focal, fibro-elastoid thickening in the coronary artery. Serious morphological changes in the pulmonary vessels such as are observed in the human pulmonary hypertension were not seen in our laboratory animals. Two dogs in each dosage group died in the course of the experiment. The results of this experiment show that it is, in general, possible to induce pulmonary hypertension by administering Aminorex orally. In two dogs, however, pressure in the pulmonary artery (measured under anaesthesia) was below 20 mm Hg (controls: 13.8 +/- 1.3 mm Hg). One possible pathogenetic mechanism underlying the pulmonary hypertension would appear to be precapillary vasoconstriction induced by Aminorex, which can lead to transient, persistent or, for some unknown reason, even permanent fixation of pulmonary resistance.

Adrenal Glands↗
PubMed1986

Polymorphic debrisoquine and mephenytoin hydroxylation in patients with pulmonary hypertension of vascular origin after aminorex fumarate.

During the period 1967 to 1971 an increase in the incidence of pulmonary hypertension of vascular origin (PHVO) was observed in Austria, Federal Republic of Germany, and Switzerland. Most patients had been given aminorex fumarate and a possible link was suspected. We therefore investigated the possibility of genetically-determined drug hydroxylation deficiencies (debrisoquine or mephenytoin type) in these patients as an explanation for the development of PHVO. Seventeen patients took 10 mg debrisoquine and 100 mg mephenytoin orally. Sixteen PHVO patients were classified as extensive metabolizers of debrisoquine with logarithmic metabolic ratios of -0.35 +/- 0.11 (mean +/- SEM), whereas one patient was a poor metabolizer with a logarithmic metabolic ratio of 1.82. For the mephenytoin hydroxylation sixteen patients with PHVO were extensive metabolizers, with logarithmic hydroxylation indices of 0.27 +/- 0.05. One poor metabolizer of mephenytoin had a logarithmic hydroxylation index of 1.59. Deficient hydroxylation of debrisoquine and mephenytoin was found in two different patients. The prevalence of poor metabolizers among patients with PHVO after aminorex fumarate was therefore approximately 9% for both debrisoquine and mephenytoin. This corresponds closely to the data of our reference population study where genetic debrisoquine and mephenytoin hydroxylation deficiencies occurred independently, with a prevalence of 10% and 5% respectively. Thus, the normal prevalence of extensive drug hydroxylation phenotypes in patients with PHVO is not consistent with the hypothesis that the development of PHVO after aminorex fumarate might be related to a pharmacogenetically determined impairment of polymorphic drug oxidation.

Adult↗
PubMedDate not supplied

Long term effects of the anorectic agent fenfluramine alone and in combination with aminorex on pulmonary and systemic circulation in the pig.

We have investigated the effects of chronic oral administration of two anorectic substances, fenfluramine and aminorex, especially on the pulmonary circulation in young pigs with one ligated pulmonary artery. The pulmonary vascular reactivity was tested by alveolar hypoxia, alveolar hyperoxia and infusion of prostaglandin F2ALPHA. No elevation of pulmonary arterial pressures or resistances were found due to the intake of fenfluramine or aminorex over a three month period. The responses to the vasoconstrictor stimuli, hypoxia and prostaglandin F2alpha, and to the vasodilator stimulus, hyperoxia, were equal and not augmented in the drug groups. Fenfluramine or aminorex could therefore could therefore not be shown to have an adverse effect on the pulmonary circulation or on the reactivity of the pulmonary vascular bed in the pig, but fenfluramine elevated systemic arterial pressure.

Aminorex↗
PubMed1997

The effects of aminorex and related compounds on brain monoamines and metabolites in CBA mice.

Acute and long-term neurochemical effects of aminorex, an appetite-suppressing drug related to amphetamine in chemical structure, and stereoisomers of its analogues were examined and compared with those of 3.4-methylenedioxymethylamphetamine (MDMA) and fenfluramine. Aminorex and its analogues, with exception of 4S, 5S-dimethylaminorex, did not cause the long-term neurotransmitter depletion in either the dopaminergic or 5-HT-ergic systems that was observed after MDMA or fenfluramine in CBA mice. These results are discussed in terms of possible structurally related mechanisms of neurotoxicity. The acute neurochemical effects showed that aminorex and analogues all produced increases in 5-hydroxytryptamine (5-HT) levels, unlike fenfluramine and MDMA in the present study or in published data. This suggests that inhibition of 5-HT metabolism, rather than direct 5-HT release, may be involved in their anorectic effect. The parallel study of acute dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) changes suggest that in CBA mice MDMA may be a better dopamine releaser and this may contribute to its dopaminergic neurotoxicity. However the ability to release dopamine or 5-HT, or both, may be important, but not the only factor involved in causing the long-term neurotoxicity observed with amphetamine derivatives.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Anorexic agents aminorex, fenfluramine, and dexfenfluramine inhibit potassium current in rat pulmonary vascular smooth muscle and cause pulmonary vasoconstriction.

BACKGROUND: The appetite suppressant aminorex fumarate is thought to have caused an epidemic of pulmonary hypertension in Europe in the 1960s. More recently, pulmonary hypertension has been described in some patients taking other amphetamine-like, anorexic agents: fenfluramine and its d-isomer, dexfenfluramine. No mechanism has been demonstrated that might account for the association between anorexic drugs and pulmonary hypertension. METHODS AND RESULTS: Using the whole-cell, patch-clamp technique, we found that aminorex, fenfluramine, and dexfenfluramine inhibit potassium current in smooth muscle cells taken from the small resistance pulmonary arteries of the rat lung. Dexfenfluramine causes reversible membrane depolarization in these cells. These actions are similar to those of hypoxia, which initiates pulmonary vasoconstriction by inhibiting a potassium current in pulmonary vascular smooth muscle. In the isolated, perfused rat lung, aminorex, fenfluramine, and dexfenfluramine induce a dose-related increase in perfusion pressure. When the production of endogenous NO is inhibited by N-nitro-L-arginine methyl ester, the pressor response to dexfenfluramine is greatly enhanced. CONCLUSIONS: These observations indicate that anorexic agents, like hypoxia, can inhibit potassium current, cause membrane depolarization, and stimulate pulmonary vasoconstriction. They suggest one mechanism that could be responsible for initiating pulmonary hypertension in susceptible individuals. It is possible that susceptibility is the result of the reduced production of an endogenous vasodilator, such as NO, but this remains speculative.

Aminorex↗
PubMed2000

Recreational use of aminorex and pulmonary hypertension.

Pulmonary hypertension has been associated with ingestion of the appetite suppressant aminorex. A similar compound, 4-methyl-aminorex (street names, "U-4-E-uh" [pronounced euphoria] or "ice"), is a "designer" drug with central stimulant activity. This drug was discovered on the property of three individuals with diagnoses of pulmonary hypertension. The association between "recreational" aminorex manufacture and ingestion and the development of pulmonary hypertension is described.

Adult↗
PubMed1985

Aminorex and pulmonary hypertension. A review.

There was an epidemic of chronic pulmonary hypertension in Austria, the Federal Republic of Germany and Switzerland, starting in 1967, peaking in 1968/69, and disappearing after 1972. The mechanism leading to pulmonary hypertension was chronic precapillary vascular obstruction due to plexogenic pulmonary arteriopathy. There was a close geographic as well as temporal relation of the epidemic to the marketing and intake of the appetite depressing drug aminorex fumarate (Menocil). 10 years after the epidemic, half of the patients have died, usually of right heart failure. Of those surviving, half present a definite regression of the pulmonary vascular obstruction. Average survival after the initial diagnosis was 3.5 years in those patients who died. Their PA pressure (+22%) and pulmonary arteriolar resistance (+40%) was higher at the onset of the observation period if compared with the corresponding values of the survivors; also the incidence of right heart failure was significantly higher (84 vs. 58%). Among the surviving patients, the only difference between those with an improved and those with a worsened haemodynamic situation was the age at the beginning of the weight-reducing treatment, those with a progression being 10 years older. The probability of survival after 10 years is considerably higher in chronic pulmonary hypertension of vascular origin (CPHVO) after aminorex than in "classical" primary pulmonary hypertension (CPHVO of unknown cause) and in CPHVO due to recurrent silent pulmonary thromboembolism. This difference in prognosis is an argument in favour of the identity of chronic pulmonary hypertension developing after the intake of the appetite depressing drug aminorex.

Adult↗
PubMed1993

[Aminorex-induced, plexogenic pulmonary arteriopathy: 25 years later!].

The purpose of this study was to examine the influence of treatment on long-term prognosis of patients with aminorex-induced plexogenic pulmonary hypertension. The study included 104 patients (13 males, 91 females) with an aminorex (menocil) intake between 1966 and 1968. All patients were treated with digitalis and diuretics, 52% received an anticoagulant medication with warfarin after pulmonary hypertension was diagnosed. During follow-up, a second right-heart catheterization was performed in 37 patients with a mean interval of 5 years. The longest mean survival time, 8.3 years, was found in patients treated with anticoagulant medication, compared to the 6.1 years found in the non-anticoagulated aminorex patients. Also, in the 5- and 10-years survival rate, patients with an anticoagulant therapy have shown better results (62.9 vs. 38% and 39 vs. 20%, respectively). Patients who received anticoagulant therapy soon after the onset of symptoms showed a better mean survival (10.9 years) than those who commenced treatment more than 1 year thereafter (mean survival 5.9 years). In 57% of the patients who had a second right-heart catheterization a decrease of pulmonary pressures could be diagnosed. Two-thirds of these patients with pulmonary pressure decrease were under anticoagulant therapy. An improvement in the NYHA-classification was seen in 44.8% of the patients treated with warfarin, in comparison to 22.2% of those who did not receive anticoagulant therapy. Although this study is retrospective, it shows a positive influence of anticoagulant therapy on survival in patients with a history of anorectic drug intake.

Adrenal Cortex Hormones↗
PubMed1971

Effect of phenmetrazine, aminorex and ( ) p-chloramphetamine on the motor activity and turnover rate of brain catecholamines.

1. The minimal doses (mumol/kg i.v.) of phenmetrazine, (+/-)-p-chloramphetamine, and aminorex which increase motor activity are 5.6, 3.5, and 1.5, respectively. We detected stereotype behaviour neither in rats receiving intravenous doses 3 times greater nor in animals injected intraperitoneally with 44, 62 and 112 mumol/kg of (+/-)-p-chloramphetamine, aminorex and phenmatrazine, respectively.2. The latter doses of the three amphetamine congeners were tested for their action on tissue monoamine content. Only (+/-)-p-chloramphetamine decreased the concentration of tel-diencephalon 5-hydroxytryptamine (5-HT) and this decrease lasted longer than 24 hours. This and the other two amphetamine congeners failed to affect the concentration of noradrenaline (NA) in brain, heart and lung.3. Aminorex (1.5 mumol/kg i.v.) and (+/-)-p-chloramphetamine (3.5 mumol/kg i.v.) decreased the turnover time of striatum dopamine (DM) but failed to change the turnover time of tel-diencephalon and brainstem NA. Phenmetrazine (5.6 mumol/kg i.v.) changed neither the turnover time of striatum DM nor that of NA in the two brain areas assayed.

Amphetamine↗
PubMed2002

Effects on serotonin in rat hypothalamus of D-fenfluramine, aminorex, phentermine and fluoxetine.

Hypothalamic 5-HT (serotonin) regulates food intake, energy expenditure and bodyweight. Using in vivo microdialysis, we determined the effects of various anorectic drugs on hypothalamic extracellular 5-HT levels during the dark phase when rats predominantly feed. Phentermine and aminorex, which were originally considered to be catecholaminergic drugs, markedly increased 5-HT efflux in rat hypothalamus. Their actions were less profound than D-fenfluramine, but considerably greater than that of the selective 5-HT reuptake inhibitor, fluoxetine. This suggests that enhanced hypothalamic 5-HT function could be involved in their anorectic actions. Pharmacological characterization revealed that D-fenfluramine, aminorex and probably also phentermine potentiate synaptic 5-HT function predominantly by release, whereas fluoxetine acts exclusively by reuptake inhibition. The results also revealed that the combined actions of phentermine and D-fenfluramine on hypothalamic extracellular 5-HT levels were additive, but not synergistic. In contrast, there was a significant negative cooperative effect on extraneuronal 5-HT of combining phentermine with fluoxetine.

Aminorex↗
PubMed1999

Aminorex, fenfluramine, and chlorphentermine are serotonin transporter substrates. Implications for primary pulmonary hypertension.

BACKGROUND: Coadministration of phentermine and fenfluramine (phen/fen) effectively treats obesity and possibly addictive disorders. The association of fenfluramine and certain other anorexic agents with serious side effects, such as cardiac valvulopathy and primary pulmonary hypertension (PPH), limits the clinical utility of these drugs. Development of new medications that produce neurochemical effects like phen/fen without causing unwanted side effects would be a significant therapeutic breakthrough. METHODS AND RESULTS: We tested the hypothesis that fenfluramine (and other anorexic agents) might increase the risk of PPH through interactions with serotonin (5-HT) transporters. Because 5-HT transporter proteins in the lung and brain are identical, we examined, in rat brain, the effects of selected drugs on 5-HT efflux in vivo and monoamine transporters in vitro as a generalized index of transporter function. Our data show that drugs known or suspected to increase the risk of PPH (eg, aminorex, fenfluramine, and chlorphentermine) are 5-HT transporter substrates, whereas drugs that have not been shown to increase the risk of PPH are less potent in this regard. CONCLUSIONS: We speculate that medications that are 5-HT transporter substrates get translocated into pulmonary cells where, depending on the degree of drug retention, their intrinsic drug toxicity, and individual susceptibility, PPH could develop as a response to high levels of these drugs or metabolites. Emerging evidence suggests that it is possible to develop transporter substrates devoid of adverse side effects. Such medications could have therapeutic application in the management of obesity, drug dependence, depression, and other disorders.

Aminorex↗
PubMed1986

[Prolonged survey of cases of pulmonary hypertension in relation to consumption of aminorex. Histological, quantitative and morphometric study of 9 cases].

The lesions of pulmonary muscular arteries of 9 female patients who died of pulmonary hypertensive disease between 9 and 17 years after intake of an anorexigenic drug, aminorex fumarate, have been examined by various methods (light microscopy, numeration of lesions, morphometry). The numeration of lesions showed the predominance of fibrotic and dilatation lesions, but also the presence of active lesions (intimal hyperplasia, plexiform lesions). Morphometry revealed an increase in mean thickness of the media, compared to that of the arteries of controls or those of a previous series, and a reduction in mean vascular volume. The existence of sclerotic lesions and reduction of vascular volume may explain the persistence of pulmonary hypertension, which fresh lesions helped to aggravate. It seems likely that functional and morphologic modifications due to the action of the drug had become self-perpetuating and may finally have induced the fatal outcome in these patients many years after intake of the slimming pill.

Adult↗