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European Journal of Pharmacology Jun 1983
Topics: Animals; Binding Sites; Cell Membrane; Corpus Striatum; Dopamine; Indoles; Mazindol; Neurons; Rats
PubMed: 6884434
DOI: 10.1016/0014-2999(83)90574-5 -
European Journal of Pharmacology Jan 2003The current studies compared mazindane (5-(4-chlorophenyl)-2,3-dihydro-5H-imidazo [2,1a] isoindole) hydrogen sulfate, a water soluble pro-drug of mazindol... (Comparative Study)
Comparative Study
The current studies compared mazindane (5-(4-chlorophenyl)-2,3-dihydro-5H-imidazo [2,1a] isoindole) hydrogen sulfate, a water soluble pro-drug of mazindol (5-(4-chlorophenyl-2,3-dihydro-5H-imidazo [2,1-a] isoindol-5-ol), with mazindol in assays used to define cocaine treatment agents. Both compounds enhanced motor activity (LMA) in Swiss Webster mice with ED(50) values of 2.5 mg/kg i.p. for mazindane and 3.9 mg/kg i.p. for mazindol. At 25 mg/kg mazindane displayed toxic effects and death while mazindol was effect/death free at 50 mg/kg. In Sprague-Dawley rats trained to discriminate cocaine from saline both compounds fully substituted for cocaine with mazindane being fourfold more potent in the total session (0.33 vs. 1.3 mg/kg i.p.) and first reinforcer (0.29 vs. 1.2 mg/kg i.p). Complete substitution was observed in rhesus monkeys trained to discriminate cocaine from saline with ED(50) values for mazindane (0.134 mg/kg i.m.) and mazindol (0.119 mg/kg i.m.). Mazindol exhibited little or no activity at 10(-5) M in inhibiting radioligand binding at 14 neurotransmitter sites while mazindane gave weak activity at the histamine H(1) and 5-hydroxytryptamine 5-HT(3) sites. These results demonstrate that mazindane could be a useful alternative to mazindol as a pharmacological tool because of its similar profile of activity and enhanced water solubility.
Topics: Analysis of Variance; Animals; Binding, Competitive; Cell Membrane; Cocaine; Discrimination Learning; Discrimination, Psychological; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Isoindoles; Macaca mulatta; Male; Mazindol; Mice; Motor Activity; Neurotransmitter Agents; Proadifen; Rats; Rats, Sprague-Dawley; Tritium
PubMed: 12504782
DOI: 10.1016/s0014-2999(02)02791-7 -
The Journal of Neuroscience : the... Jun 1985Mazindol is a potent inhibitor of neuronal dopamine (DA) and norepinephrine (NE) uptake. DA and NE uptake sites in rat brain have been differentially visualized using...
Mazindol is a potent inhibitor of neuronal dopamine (DA) and norepinephrine (NE) uptake. DA and NE uptake sites in rat brain have been differentially visualized using [3H]mazindol autoradiography. At appropriate concentrations, desipramine (DMI) selectively inhibits [3H]mazindol binding to NE uptake sites without significantly affecting binding to DA uptake sites. The localization of DMI-insensitive specific [3H] mazindol binding, reflecting DA uptake sites, is densest in the caudate-putamen, the nucleus accumbens, the olfactory tubercle, the subthalamic nucleus, the ventral tegmental area, the substantia nigra (SN) pars compacta, and the anterior olfactory nuclei. In contrast, the localization of DMI-sensitive specific [3H]mazindol binding, representing NE uptake sites, is densest in the locus coeruleus, the nucleus of the solitary tract, the bed nucleus of the stria terminalis, the paraventricular and periventricular nuclei of the hypothalamus, and the anteroventral thalamus. The distribution of DMI-insensitive specific [3H]mazindol binding closely parallels that of dopaminergic terminal and somatodendritic regions, while the distribution of DMI-sensitive specific [3H]mazindol binding correlates well with the regional localization of noradrenergic terminals and cell bodies. Injection of 6-hydroxydopamine, ibotenic acid, or colchicine into the SN decreases [3H]mazindol binding to DA uptake sites in the ipsilateral caudate-putamen by 85%. In contrast, ibotenic acid lesions of the caudate-putamen do not reduce [3H]mazindol binding to either the ipsilateral or contralateral caudate-putamen. Thus, the DA uptake sites in the caudate-putamen are located on the presynaptic terminals of dopaminergic axons originating from the SN.
Topics: Animals; Autoradiography; Brain; Corpus Striatum; Desipramine; Dopamine; Indoles; Male; Mazindol; Norepinephrine; Rats; Rats, Inbred Strains; Tritium
PubMed: 4009243
DOI: 10.1523/JNEUROSCI.05-06-01513.1985 -
Journal of Neural Transmission 1979Mazindol, an anorexic drug, caused a large increase in brain 3, 4-dihydroxyphenylacetic acid (DOPAC) concentration in spiperone-pretreated rats. The increase was...
Mazindol, an anorexic drug, caused a large increase in brain 3, 4-dihydroxyphenylacetic acid (DOPAC) concentration in spiperone-pretreated rats. The increase was dose-related over a 1--10 mg/kg dose range of mazindol and was maximum within 1 hour after maxzindol injection into rats pretreated 1 hour previously with spiperone. In spiperone-pretreated rats, mazindol accelerated the disappearance of dopamine after the inhibition of dopamine synthesis by alpha-methyltyrosine. Mazindol apparently resembles amfonelic acid, methylphenidate, and cocaine in facilitating the impulse-mediated release of dopamine.
Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Brain; Butyrophenones; Dopamine; Dose-Response Relationship, Drug; Drug Interactions; Indoles; Male; Mazindol; Naphthyridines; Rats; Spiperone
PubMed: 438800
DOI: 10.1007/BF01252698 -
Journal of Pharmacological and... 2016Even after removal of some stimulants, like fenproporex, amfepramone and mazindol, from Brazilian market, the use of these substances is still high, especially by...
INTRODUCTION
Even after removal of some stimulants, like fenproporex, amfepramone and mazindol, from Brazilian market, the use of these substances is still high, especially by drivers. Mazindol is the second most used anorectic agent in the world acting as an indirect sympathomimetic agonist, having stimulatory action on central nervous system. Plasma is a good matrix to monitor since it reflects the psychomotor effects of these drugs, but unlike urine has an invasive collection; drug levels and detection time are quite low.
METHOD
The method involved a liquid-liquid extraction of the samples and a LC-MS analysis was fully validated. Method was used to analyze samples of urine and plasma collected from health volunteers in a period of 24h. Metabolite of mazindol was synthesized using alkaline conditions.
RESULTS
After validation the method proved to be adequate to analyze samples collected from health volunteers. Method was linear in the concentration range of 0.1-10ng/mL (r=0.9982) for plasma and 5-50ng/mL (r=0.9973) for urine.
DISCUSSION
Analysis of the samples showed that mazindol can be detected after 1h of administration and that concentration levels in urine were always higher than in plasma. Mazindol metabolite was detected only in urine.
Topics: Central Nervous System Stimulants; Chromatography, Liquid; Humans; Liquid-Liquid Extraction; Mazindol; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 26718151
DOI: 10.1016/j.vascn.2015.12.003 -
Neuroscience Letters Jan 2000Our previous studies showed that monkey amniotic epithelial cells (MAEC) synthesize and release catecholamines and possess D1 and D2 dopamine (DA) receptors (Elwan,...
Our previous studies showed that monkey amniotic epithelial cells (MAEC) synthesize and release catecholamines and possess D1 and D2 dopamine (DA) receptors (Elwan, M.A., Ishii, T., Ono, F. and Sakuragawa, N., Evidence for the presence of dopamine D1 receptor mRNA and binding sites in monkey amniotic epithelial cells. Neurosci. Lett., 262 (1999) 9-12; Elwan, M.A., Ishii, T. and Sakuragawa, N., Detection of dopamine D2 receptor mRNA and binding sites in monkey amniotic epithelial cells. J. Neurosci. Res., 56 (1999) 316-322; Elwan, M.A., Thangavel, R., Ono, F. and Sakuragawa, N., Synthesis and release of catecholamines by cultured monkey amniotic epithelial cells. J. Neurosci. Res., 53 (1998) 107-113). In the present study we tested the presence of DA transporter (DAT) in MAEC using radioligand binding experiments. Saturation studies showed that [3H]mazindol binds to a high affinity site with K(D) and Bmax values of 7.85 +/- 1.25 nM and 123.22 +/- 18.34 fmol/mg protein, respectively. Competition studies indicated that selective DAT inhibitors are potent displacers of [3H]mazindol binding, compared to inhibitors of other types of transporters. The rank order of potency of the competing drugs is consistent with the pharmacology of DAT. These results provide, for the first time, clear evidence that MAEC natively possess DAT binding sites and suggest that MAEC may provide a potential primate cell model to study DA release and uptake processes and to explore new drugs active at this site.
Topics: Amniotic Fluid; Animals; Binding Sites; Cell Culture Techniques; Dopamine; Dopamine Uptake Inhibitors; Epithelial Cells; Female; Macaca; Mazindol; Radioligand Assay; Receptors, Dopamine
PubMed: 10670782
DOI: 10.1016/s0304-3940(99)00938-6 -
General Dentistry 1997
Review
Topics: Adult; Appetite Depressants; Benzphetamine; Dental Care for Chronically Ill; Dental Caries; Diethylpropion; Drug Interactions; Female; Fenfluramine; Humans; Male; Mazindol; Morpholines; Obesity; Periodontal Diseases; Phentermine; Phenylpropanolamine; Pregnancy; Xerostomia
PubMed: 9515435
DOI: No ID Found -
Clinical and Experimental Pharmacology... 19961. The anti-obesity and anti-diabetic effects of mazindol were evaluated in obese diabetic yellow KK mice and C57Bl control mice. 2. The study compound was fed through a...
1. The anti-obesity and anti-diabetic effects of mazindol were evaluated in obese diabetic yellow KK mice and C57Bl control mice. 2. The study compound was fed through a gastric tube at a rate of 1 or 2 mg/kg per day (0.01 mol/L HCl as control) for 2 weeks. The following parameters were compared in treated and control animals: bodyweight, food intake, white adipose tissue (WAT) weight, brown adipose tissue (BAT) weight and its thermogenesis, noradrenaline (NA) turnover, blood glucose and serum insulin levels and glucose transporter 4 (GLUT4). 3. Furthermore, bodyweight loss of mice pair-fed the same amount of food as the mazindol-treated mice for 2 weeks was measured. 4. Mazindol significantly decreased food intake and significantly increased guanosine-5'-diphosphate-binding in BAT mitochondria and NA turnover in BAT in both yellow KK and C57Bl groups. The amounts of WAT in subcutaneous, mesenteric and retroperitoneal regions and bodyweights were significantly decreased in both groups. Bodyweight loss in mice pair fed with the mazindol-treated groups was approximately 70% compared with that in the mazindol-treated groups. Furthermore, mazindol decreased the levels of blood glucose and serum insulin during the glucose overloading test in yellow KK mice, but it did not influence the GLUT4 protein concentration in WAT and muscle. 5. These observations suggest that mazindol possesses both an anti-obesity action, due to the inhibition of appetite as well as the activation of BAT thermogenesis via increased NA turnover in BAT, and an anti-diabetic action. Consequently, mazindol may be useful for the treatment of obesity as well as non-insulin-dependent diabetes mellitus in obese persons.
Topics: Adipose Tissue; Adipose Tissue, Brown; Animals; Anti-Obesity Agents; Appetite Depressants; Blood Glucose; Blotting, Western; Body Temperature Regulation; Body Weight; Eating; Female; Glucose Transporter Type 4; Hypoglycemic Agents; Insulin; Mazindol; Mice; Mice, Inbred C57BL; Mice, Obese; Monosaccharide Transport Proteins; Muscle Proteins; Muscle, Skeletal; Norepinephrine
PubMed: 8800569
DOI: 10.1111/j.1440-1681.1996.tb02764.x -
Pharmacology, Biochemistry, and Behavior Oct 1986Amphetamine, diethylpropion and mazindol were administered to rats in both acute and chronic experiments to measure the changes in purine nucleotide (GDP) binding to the...
Amphetamine, diethylpropion and mazindol were administered to rats in both acute and chronic experiments to measure the changes in purine nucleotide (GDP) binding to the mitochondria from interscapular brown adipose tissue. There was a dose-dependent response to acute treatment with mazindol, but no such effect with diethylpropion. The effects of mazindol and amphetamine were present as early as 3 hours after treatment, and persisted for at least 48 hours, when compared to vehicle-injected rats when all rats were fasted from the time of injection until study. There was no effect when these drugs were added in vitro to mitochondria from brown adipose tissue. Diethylpropion had no effect on GDP binding either in vivo or in vitro at any of the times tested. Following 11 days of treatment with diethylpropion, amphetamine or mazindol, there was a significant increase in purine nucleotide (GDP) binding to mitochondria only in the amphetamine-treated animals. There was no difference in body weight or food intake with any of the three drugs after the third day of chronic treatment. The differences between the effects of these three drugs and those of fenfluramine are discussed in terms of their different central mechanisms of action.
Topics: Adipose Tissue, Brown; Animals; Body Weight; Dextroamphetamine; Diethylpropion; Dose-Response Relationship, Drug; Female; Guanine Nucleotides; Guanosine Diphosphate; Indoles; Mazindol; Mitochondria; Rats; Rats, Inbred Strains
PubMed: 3786335
DOI: 10.1016/0091-3057(86)90378-3 -
British Medical Journal (Clinical... Dec 1983
Topics: Adult; Humans; Indoles; Male; Mazindol; Middle Aged; Pain; Testicular Diseases
PubMed: 6416584
DOI: 10.1136/bmj.287.6407.1763