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Lancet (London, England) Jan 1988
Clinical Trial
Topics: Child; Clinical Trials as Topic; Heart Rate; Humans; Indoles; Male; Mazindol; Muscular Dystrophies
PubMed: 2893022
DOI: 10.1016/s0140-6736(88)92759-6 -
Neuroscience Letters Jan 1992The effect of mazindol on the dopamine (DA) uptake system in the rat striatum was studied by in vivo voltammetry and microdialysis. An increase in the maximal uptake... (Comparative Study)
Comparative Study
The effect of mazindol on the dopamine (DA) uptake system in the rat striatum was studied by in vivo voltammetry and microdialysis. An increase in the maximal uptake rate was observed by voltammetry 30 min after i.p. administration of 1, 5, 10, 15, and 20 mg/kg doses but not after a dose of 25 mg/kg, while stimulated release was enhanced at all doses. The increased maximal uptake is in contrast to increased levels of extracellular DA observed with microdialysis following mazindol administration. This divergence of action is anomalous in the context of current understanding of the DA uptake system.
Topics: Animals; Corpus Striatum; Dialysis; Dopamine; Dose-Response Relationship, Drug; Electric Stimulation; Electrochemistry; Kinetics; Male; Mazindol; Rats; Rats, Inbred Strains; Reference Values
PubMed: 1589149
DOI: 10.1016/0304-3940(92)90523-a -
Journal of Medicinal Chemistry Sep 2002A series of mazindol (2) and homomazindol (3) analogues with a variety of electron-donating and electron-withdrawing groups in the pendant aryl group and the benzo ring...
A series of mazindol (2) and homomazindol (3) analogues with a variety of electron-donating and electron-withdrawing groups in the pendant aryl group and the benzo ring C, as well as H, methoxy, and alkyl groups replacing the hydroxyl group were synthesized, and their binding affinities at the dopamine transporter (DAT) on rat or guinea pig striatal membranes were determined. Several active analogues were also evaluated for their ability to block uptake of DA, 5-HT, and NE and inhibit binding of [(125)I] RTI-55 at HEK-hDAT, HEK-hSERT, and HEK-hNET cells. Mazindane (26) was found to be a pro-drug, oxidizing (5-H --> 5-OH) to mazindol on rat striatal membranes and HEK-hDAT cells. The 4',7,8-trichloro analogue (38) of mazindol was the most potent and selective ligand for HEK-hDAT cells (DAT K(i) = 1.1 nM; SERT/DAT = 1283 and NET/DAT = 38). Experimental results strongly favor the cyclic or ol tautomers of 2 and 3 to bind more tightly at the DAT than the corresponding keto tautomers.
Topics: Animals; Binding Sites; Cell Line; Central Nervous System Stimulants; Cocaine; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Dopamine Uptake Inhibitors; Guinea Pigs; Humans; In Vitro Techniques; Isoindoles; Male; Mazindol; Membrane Glycoproteins; Membrane Transport Modulators; Membrane Transport Proteins; Nerve Tissue Proteins; Prodrugs; Radioligand Assay; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship
PubMed: 12213053
DOI: 10.1021/jm010302r -
Neuroscience Letters Oct 2016In this study, we evaluated the preventive effect of mazindol on the development of obesity and sought to elucidate the drug's effects on the reward system. In mice,...
In this study, we evaluated the preventive effect of mazindol on the development of obesity and sought to elucidate the drug's effects on the reward system. In mice, body weight gain and hyperphagia induced by high-fat diet (HFD) were decreased by 38.6% and 13.9%, respectively, by subcutaneous infusion of mazindol (1.5mg/kg/day) for 28days. A single intraperitoneal administration of mazindol (1.5mg/kg) significantly reduced lipid preference, as assessed using the two-bottle preference paradigm (vehicle, 89.98±1.66%; mazindol, 75.65±5.47%; p<0.05). In addition, the conditioned place preference (CPP) test demonstrated that mazindol (1.5mg/kg) significantly decreased CPP score for HFD as compared with vehicle (vehicle, 330.44±58.61s; mazindol, 144.72±43.02s; p<0.05). Moreover, at the dose required for these effects, mazindol did not elicit abuse potential or induce psychostimulant-like behavior. These results confirm that mazindol prevents diet-induced obesity without addictive behavior and demonstrate that its action is mediated at least in part via the reward system, advancing our understanding of mazindol in clinical practice.
Topics: Animals; Anti-Obesity Agents; Conditioning, Psychological; Dietary Fats; Drug Tolerance; Food Preferences; Infusions, Subcutaneous; Male; Mazindol; Mice, Inbred C57BL; Motor Activity; Reward
PubMed: 27658895
DOI: 10.1016/j.neulet.2016.09.014 -
Muscle & Nerve Dec 1990There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo. The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy.
Topics: Behavior; Double-Blind Method; Feeding and Eating Disorders; Humans; Male; Mazindol; Muscle Contraction; Muscular Dystrophies; Time Factors; Xerostomia
PubMed: 2266990
DOI: 10.1002/mus.880131212 -
Journal of Neurochemistry Jun 1999The formation of hydroxyl radicals following the systemic administration of 3,4-methylenedioxymethamphetamine (MDMA) was studied in the striatum of the rat by...
The formation of hydroxyl radicals following the systemic administration of 3,4-methylenedioxymethamphetamine (MDMA) was studied in the striatum of the rat by quantifying the stable adducts of salicylic acid and D-phenylalanine, namely, 2,3-dihydroxybenzoic acid (2,3-DHBA) and p-tyrosine, respectively. The repeated administration of MDMA produced a sustained increase in the extracellular concentration of 2,3-DHBA and p-tyrosine, as well as dopamine. The MDMA-induced increase in the extracellular concentration of both dopamine and 2,3-DHBA was suppressed in rats treated with mazindol, a dopamine uptake inhibitor. Mazindol also attenuated the long-term depletion of serotonin (5-HT) in the striatum produced by MDMA without altering the acute hyperthermic response to MDMA. These results are supportive of the view that MDMA produces a dopamine-dependent increase in the formation of hydroxyl radicals in the striatum that may contribute to the mechanism whereby MDMA produces a long-term depletion of brain 5-HT content.
Topics: Animals; Corpus Striatum; Hydroxybenzoates; Hydroxyl Radical; Kinetics; Male; Mazindol; Microdialysis; N-Methyl-3,4-methylenedioxyamphetamine; Phenylalanine; Rats; Rats, Sprague-Dawley; Salicylic Acid; Serotonin; Tyrosine
PubMed: 10349862
DOI: 10.1046/j.1471-4159.1999.0722516.x -
Molecular Pharmacology Jul 1984[3H]Mazindol labels neuronal dopamine uptake sites in corpus striatum membranes (KD = 18 nM) and neuronal norepinephrine uptake sites in cerebral cortex and...
[3H]Mazindol labels neuronal dopamine uptake sites in corpus striatum membranes (KD = 18 nM) and neuronal norepinephrine uptake sites in cerebral cortex and submaxillary/sublingual gland membranes (KD = 4 nM). The potencies of various inhibitors of biogenic amine uptake in reducing [3H]mazindol binding in striatal membranes correlate with their potencies for inhibition of neuronal [3H]dopamine accumulation, whereas their potencies in reducing [3H]mazindol binding to cortical and salivary gland membranes correlate with their potencies for inhibition of neuronal [3H]norepinephrine accumulation. Similar to the dopamine and norepinephrine uptake systems, [3H]mazindol binding in all three tissues is dependent upon sodium (with potassium, lithium, rubidium, and Tris being ineffective substitutes) and chloride (with sulfate and phosphate being ineffective substitutes). In membranes of the cerebral cortex and salivary gland, half-maximal stimulation is observed at 50-80 mM NaCl, whereas in membranes of the corpus striatum half-maximal stimulation occurs at 240 mM NaCl. In striatal membranes NaCl increases the affinity of [3H]mazindol binding with no effect on the maximal number of sites. The enhancement of affinity is due to a selective slowing of the dissociation of the ligand from its binding site. The association of [3H]mazindol binding sites with neuronal dopamine uptake sites in the corpus striatum is further supported by the reduction of [3H]mazindol binding sites in striatal membranes following destruction of dopaminergic neurons by 6-hydroxydopamine. Similarly, the association of [3H]mazindol binding sites with neuronal norepinephrine uptake sites in cerebral cortex is supported by the reduction of [3H]mazindol binding to cortical membranes following destruction of noradrenergic neurons by N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine.
Topics: Animals; Binding, Competitive; Biological Transport; Cell Membrane; Corpus Striatum; Dopamine; Indoles; Kinetics; Male; Mazindol; Neurons; Norepinephrine; Rats; Rats, Inbred Strains; Receptors, Adrenergic; Receptors, Dopamine; Sublingual Gland; Submandibular Gland
PubMed: 6087116
DOI: No ID Found -
Israel Journal of Medical Sciences Jan 1989In the search for mechanisms supporting the weight-reducing effect of mazindol, we examined the influence of the drug on metabolism and gastric evacuation in two groups... (Clinical Trial)
Clinical Trial
In the search for mechanisms supporting the weight-reducing effect of mazindol, we examined the influence of the drug on metabolism and gastric evacuation in two groups of 10 women each. In the first group the effect of mazindol on thermogenesis was assessed by indirect calorimetry, and blood glycerol concentration was taken as an index of lipolysis. After oral administration of 2 mg mazindol no significant changes were observed in the energy expenditure or lipolysis, either at rest or during exercise. In the second group, the influence of 2 mg mazindol, taken orally, on gastric emptying (GE) of a radiolabeled solid meal was examined with the use of a gamma camera. The drug significantly inhibited GE--the median GEt1/2 was 119 min after placebo vs. 230 min after mazindol. The mean +/- SE of the emptying index was 1.13 +/- 0.26 min-1 after placebo vs. 0.53 +/- 0.14 min-1 after mazindol. Mazindol elicited a delaying effect on the late phase of GE, as confirmed by a significant decrease of the shape parameter (S) of the power-exponential fitted GE curves, 2.09 +/- 0.22 after placebo vs. 1.61 +/- 0.24 after mazindol, and by the comparison of the amount of food emptied from the stomach: 30.7 +/- 6.1% after placebo vs. 17.8 +/- 4.0% after mazindol, at 80 min, and 38.9 +/- 6.2% after placebo vs. 20.6 +/- 4.3% after mazindol, at 90 min of the GE measurement.
Topics: Adult; Energy Metabolism; Female; Gastric Emptying; Glycerol; Humans; Indoles; Mazindol
PubMed: 2925353
DOI: No ID Found -
Archives of Neurology Dec 1983Mazindol, a drug that blocks the reuptake of dopamine, was studied in the treatment of Parkinson's disease in both a pilot study (12 patients) and a controlled trial (11... (Clinical Trial)
Clinical Trial
Mazindol, a drug that blocks the reuptake of dopamine, was studied in the treatment of Parkinson's disease in both a pilot study (12 patients) and a controlled trial (11 patients). The patients had stage II or III disease, according to the classification of Hoehn and Yahr. Both studies showed that mazindol possessed anti-parkinsonian properties and that the improvement was statistically significant. The therapeutic effect was moderate, but could be of value for patients in the early stages of the disease. The drug was well tolerated; only two patients had side effects.
Topics: Clinical Trials as Topic; Double-Blind Method; Female; Humans; Indoles; Male; Mazindol; Parkinson Disease; Pilot Projects
PubMed: 6357158
DOI: 10.1001/archneur.1983.04050120038004 -
Journal of Psychopharmacology (Oxford,... Jul 2008The aim of the present study was to determine the impact of the appetite suppressant mazindol on meal pattern in rats. Meal patterns were monitored in adult male rats...
The aim of the present study was to determine the impact of the appetite suppressant mazindol on meal pattern in rats. Meal patterns were monitored in adult male rats after mazindol dosing during the first three hours of the dark cycle using automated feeding chambers (BioDAQ). Mazindol (0, 0.25, 1.25 and 2.5 mg/kg, IP) produced a dose-dependent hypophagia and hypodipsia. Meal size and meal number were significantly suppressed by mazindol. The meal pattern findings indicate that mazindol inhibits eating in the rat via a suppression of both meal size and meal number.
Topics: Animals; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Eating; Feeding Behavior; Male; Mazindol; Rats; Rats, Sprague-Dawley
PubMed: 18208906
DOI: 10.1177/0269881107083837