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1.
Magí Farré María-Teresa Terán Pere N. Roset Marta Mas Marta Torrens J. Camí 《Psychopharmacology》1998,140(4):486-495
Abuse liability and acute subjective and psychomotor effects of flunitrazepam were assessed in ten methadone-maintained males
with history of benzodiazepine and alcohol use, who voluntarily participated in a double-blind, controlled, cross-over, randomized
clinical trial. There were six experimental sessions in which a single oral dose of flunitrazepam 1, 2, and 4 mg; triazolam
0.5 and 0.75 mg; and placebo was given. Evaluations included physiological measures; psychomotor performance tasks (simple
reaction time, Digit Symbol Substitution Test, balance task, Maddox-wing device); and self-administered subjective effects
questionnaires [Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS), a series of visual analog scales
(VAS)]. All drugs but flunitrazepam 1 mg caused an impairment of psychomotor tasks. Effects were more evident with the highest
doses of both drugs. Only flunitrazepam 4 mg produced a significant decrease in balance time. Triazolam 0.75 mg induced increases
in sedation measured by ARCI-PCAG, depression in POMS, and VAS-drowsiness scores. Flunitrazepam 4 mg caused euphoria-related
effects as measured by increases in ARCI-MBG and “high” scores in the VAS. Our findings of flunitrazepam-induced euphoria
in methadone-maintained subjects together with epidemiological evidence of flunitrazepam abuse by opioid dependents, suggest
that it may be included in the group of benzodiazepines with a relatively high abuse potential.
Received: 13 February 1998/Final version: 1 May 1998 相似文献
2.
Pacifici R Zuccaro P Farré M Pichini S Di Carlo S Roset PN Ortuño J Segura J Hernández-López C De La Torre R 《Annali dell'Istituto superiore di sanità》2000,36(1):69-75
In vitro exposure to ecstasy (3,4-methylenedioxymethamphetamine, MDMA) alters some immune parameters such as T-cell regulatory function, cytotoxic T-lymphocyte activity, natural killer cell activity and macrophage function. Administration of MDMA in rats produces a suppression of lympho-proliferation response and a decrease in circulating lymphocytes, accompanied by an increase in plasma corticosterone. It was postulated a direct action of MDMA on lymphocytes or rather an indirect action mediated by the hypothalamic pituitary adrenal axis (HPA-AXIS) and/or the sympathetic nervous system (SNS). Acute MDMA treatment effected on healthy-volunteers produces an immune dysfunction associated with pharmaceutical characteristics and so with MDMA plasma concentrations. There is a decrease in CD4+ T-cells and functional responsiveness of lymphocytes, while percentage of natural killer cells increases. A contemporary rise of cortisol plasma concentrations supports the hypothesis of MDMA-induced release of corticotrophin-releasing factor from the hypothalamus and subsequent HPA-axis and SNS activation. 相似文献
3.
Barceló Bernardino Gomila Isabel Rotolo Maria Concetta Marchei Emilia Kyriakou Chrystalla Pichini Simona Roset Carolina Elorza Miguel Ángel Busardò Francesco Paolo 《International journal of legal medicine》2017,131(6):1543-1553
International Journal of Legal Medicine - The acute and chronic toxicity of several new psychoactive substances (NPS) is unknown, and only little information is available on the pharmacology and... 相似文献
4.
Javier Jacob
scar Mir Carles Ferre Carmen Borraz‐Ords Guillermo Llopis‐García Rosa Comabella Jos María Fernndez‐Caadas Amparo Mercado Alex Roset Fernando Richard‐Espiga Amparo Valero‐Domnech Jos Luis Martínez‐Gimeno Francisco Javier Martín‐Snchez Pere Llorens Pablo Berrocal‐Gil María Jos Prez‐Dur Jos María lvarez‐Prez Pilar Lpez‐Díez Pablo Herrero‐Puente Josep Comín‐Colet 《International journal of clinical practice》2020,74(10)
5.
Badia X Mearin F Balboa A Baró E Caldwell E Cucala M Díaz-Rubio M Fueyo A Ponce J Roset M Talley NJ 《PharmacoEconomics》2002,20(11):749-758
OBJECTIVES: To evaluate the burden of illness in irritable bowel syndrome (IBS), in terms of resource utilisation (direct and indirect) and health-related quality of life (HR-QOL), in individuals with IBS who meet Rome I and Rome II criteria. METHODS: A cross-sectional study, carried out by personal interview, on a representative sample (n = 2000) of the Spanish population. Individuals with suspected IBS were identified via a screening question and subsequently given an epidemiological questionnaire to complete. The questionnaire collected information on IBS symptoms, resource utilisation, and HR-QOL [Medical Outcomes Study 36-item Short Form (SF-36)]. RESULTS: Sixty-five individuals met Rome II criteria for IBS, while 146 individuals met exclusively Rome I criteria. Of Rome II individuals, 67.7% had consulted some type of healthcare professional in the previous 12 months, compared with only 41.8% of those individuals meeting exclusively Rome I criteria (p vs 17.1%); 'drug consumption' (70.8 vs 45.2%); and 'reduced performance in main activity' (60 vs 27.4%). Compared with the general population, the study sample reported significantly worse HR-QOL scores in four dimensions of the SF-36 ('bodily pain', 'vitality', 'social functioning' and 'role-emotional'. Additionally, individuals meeting Rome II criteria reported worse HR-QOL scores than those individuals meeting exclusively Rome I criteria, especially in the 'bodily pain' and 'general health' dimensions. CONCLUSIONS: The burden of illness in IBS is important and correlated to the diagnostic criteria employed. Individuals who met Rome II criteria reported a higher level of resource utilisation and worse HR-QOL than individuals meeting exclusively Rome I criteria. 相似文献
6.
de la Torre R Farré M Ortuño J Mas M Brenneisen R Roset PN Segura J Camí J 《British journal of clinical pharmacology》2000,49(2):104-109
AIMS: 3,4-Methylenedioxymethamphetamine (MDMA, commonly called ecstasy) is a synthetic compound increasingly popular as a recreational drug. Little is known about its pharmacology, including its metabolism and pharmacokinetics, in humans in controlled settings. A clinical trial was designed for the evaluation of MDMA pharmacological effects and pharmacokinetics in healthy volunteers. METHODS: A total of 14 subjects were included. In the pilot phase six received MDMA at 50 (n=2), 100 (n=2), and 150 mg (n=2). In the second phase eight received MDMA at both 75 and 125 mg (n=8). Subjects were phenotyped for CYP2D6 activity and were classified as extensive metabolizers for substrates, such as MDMA, whose hepatic metabolism is regulated by this enzyme. Plasma and urine samples were collected throughout the study for the evaluation of MDMA pharmacokinetics. Body fluids were analysed for the determination of MDMA and its main metabolites 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxy-methamphetamine (HMMA) and 4-hydroxy-3-methoxy-amphetamine (HMA). RESULTS: As the dose of MDMA administered was increased, volunteers showed rises in MDMA concentrations that did not follow the same proportionality which could be indicative of nonlinearity. In the full range of doses tested the constant recovery of HMMA in the urine combined with the increasing MDMA recovery seems to point towards a saturation or an inhibition of MDMA metabolism (the demethylenation step). These observations are further supported by the fact that urinary clearance was rather constant while nonrenal clearance was dose dependent. CONCLUSIONS: It has previously been postulated that individuals genetically deficient for the hepatic enzyme CYP2D6 (about 10% of the Caucasian people) were at risk of developing acute toxicity at moderate doses of MDMA because the drug would accumulate in the body instead of being metabolized and inactivated. The lack of linearity of MDMA pharmacokinetics (in a window of doses compatible with its recreational use) is a more general phenomenon as it concerns the whole population independent of their CYP2D6 genotype. It implies that relatively small increases in the dose of MDMA ingested are translated to disproportionate rises in MDMA plasma concentrations and hence subjects are more prone to develop acute toxicity. 相似文献
7.
M Dehan M C Imbert J P Gautier C Benisvy F Roset J F Magny M A Saby P Dworzak H Guyot J L Chabernaud 《Archives fran?aises de pédiatrie》1988,45(8):541-548
A proper organization has been set up at Antoine-Béclère's hospital in order to study the infants who died suddenly. Between July 1985 and July 1987, 69 cases (10 babies less than 1 week of age) were admitted. The purpose of this work was, for the 59 sudden deaths of infants aged more than 1 week (35 males, 24 females), to present the results of a definite protocol of investigation (past history, clinical examination, laboratory and pathological data) for determining either the etiology or the mechanism of these deaths. A thorough investigation was performed in 45/52 cases (no autopsy in 7 cases). A definite diagnosis was possible in 38/45: 13 viral infections, 5 gastro-esophageal reflux, 13 viral infections associated with reflux, 9 with an additional event (massive alimentary inhalation, slipping under blankets, major hyperthermia) to either a viral infection or a reflux, 1 cardiac malformation, 1 metabolic disorder, 2 accidents and 1 infanticide. With this protocol, 7/45 deaths remained unexplained. This medical approach of the problem of sudden deaths in infants is beneficial to the counselling of the parents and to the management of subsequent children. 相似文献
8.
Nieves Pizarro Magí Farré Mitona Pujadas Ana Ma Peiró Pere N Roset Jesús Joglar Rafael de la Torre 《Drug metabolism and disposition》2004,32(9):1001-1007
3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a designer drug commonly misused in large segments of young populations. MDMA is usually formulated in tablets of its racemate (1:1 mixture of its enantiomers) in doses ranging from 50 to 200 mg. MDMA has an enantioselective metabolism, the (S)-enantiomer being metabolized faster than the (R)-enantiomer. Different pharmacologic properties have been attributed to each enantiomer. The carbon responsible for MDMA chirality is preserved along its metabolic disposition. An analytical method has been developed to determine MDMA enantiomers and those from its major metabolites, 3,4-methylenedioxyamphetamine (MDA), 3,4-dihydroxymeth-amphetamine (HHMA), and 4-hydroxy-3-methoxymethamphet-amine (HMMA). It has been applied to the analysis of plasma and urine samples from healthy recreational users of MDMA who participated voluntarily in a clinical trial and received 100 mg (R,S)-MDMA. HCl orally. (R)/(S) ratios both in plasma (0-48 h) and urine (0-72 h) for MDMA and MDA were >1 and <1, respectively. Ratios corresponding to HHMA and HMMA, close to unity, deviate from theoretical expectations and are most likely explained by the ability of MDMA to autoinhibit its own metabolism. The short elimination half-life of (S)-MDMA (4.8 h) is consistent with the subjective effects and psychomotor performance reported in subjects exposed to MDMA, whereas the much longer half-life of the (R)-enantiomer (14.8 h) correlates with mood and cognitive effects experienced on the next days after MDMA use. 相似文献
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