Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sleep-related eating disorders distinct from daytime eating disorders have recently been shown to be associated with sleepwalking (SW), periodic limb movement (PLM) disorder and triazolam abuse in a series of 19 adults. We now report eight other primary or combined etiologies identified by clinical evaluations and polysomnographic monitoring of 19 additional adults (mean age 40 years; 58% female): i) obstructive sleep apnea (OSA), with eating during apnea-induced confusional arousals (n = 3); ii) OSA-PLM disorder (n = 1); iii) familial SW and sleep-related eating (n = 2); iv) SW-PLM disorder (n = 1); v) SW-irregular sleep/wake pattern disorder (n = 1); vi) familial restless legs syndrome and sleep-related eating (n = 2); vii) anorexia nervosa with nocturnal bulimia (n = 2) and viii) amitriptyline treatment of migraines (n = 1). In our cumulative series of 38 patients (excluding six with simple obesity from daytime overeating), 44% were overweight (i.e. > 20% excess weight) from sleep-related eating. Nightly sleep-related binge eating (without hunger or purging) had occurred in 84% of patients. Onset of sleep-related eating was also closely linked with i) acute stress involving reality-based concerns about the safety of family members or about relationship problems (n = 6), ii) abstinence from alcohol and opiate/cocaine abuse (n = 2) and iii) cessation of cigarette smoking (n = 2). Current treatment data indicate a primary role of dopaminergic agents (carbidopa/L-dopa; bromocriptine), often combined with codeine and clonazepam, in controlling most cases involving SW and/or PLM disorder. Fluoxetine was effective in two of three patients. Nasal continuous positive airway pressure therapy controlled sleep-related eating in two OSA patients.
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PMID:Additional categories of sleep-related eating disorders and the current status of treatment. 810 56

The combined administration of phentermine and fenfluramine (PHEN/FEN) has been used as a treatment for obesity. Recent evidence suggests that this drug mixture may also be an effective medication for substance abuse disorders, including cocaine dependence. It is well-established that repeated high-dose fenfluramine causes serotonin (5-HT) terminal degeneration in laboratory animals, and no studies have addressed possible interactions between phentermine and fenfluramine. The purpose of the present work was to examine the effect of phentermine coadministration on fenfluramine-induced depletion of 5-HT in mouse forebrain. In addition, because of the potential for cocaine abuse in drug addicts taking PHEN/FEN as a medication, we examined the effects of PHEN/FEN on forebrain 5-HT levels in the presence or absence of cocaine. Fenfluramine (0, 3, 10, 30 mg/kg, s.c. twice daily for 4 days) caused a dose-dependent reduction in forebrain 5-HT without affecting dopamine or norepinephrine. Phentermine coadministration (7 mg/kg, s.c. twice daily for 4 days) did not significantly alter the 5-HT-depleting effect of fenfluramine. Likewise, cocaine (10 mg/kg, i.p.), administered 60 min prior to or 60 min after PHEN/FEN, had no effect on the PHEN/FEN-induced decrease in central 5-HT. The present results indicate that doses of phentermine far above those typically administered to humans do not potentiate the 5-HT-depleting effect of repeated high-dose fenfluramine. Moreover, exposure to cocaine does not significantly alter the long-term neurochemical actions of the PHEN/FEN mixture.
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PMID:Effects of phentermine and cocaine on fenfluramine-induced depletion of serotonin in mouse brain. 879 12

Chemically, TDIQ (5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline) can be viewed as a conformationally restricted phenylalkylamine that is related in structure to amphetamine but does not stimulate (or depress) locomotor activity in rodents. In radioligand binding studies TDIQ displays selective affinity for alpha(2)-adrenergic receptor subsites (i.e., alpha(2A)-, alpha(2B)-, and alpha(2C)-adrenergic receptors), and behavioral data suggest that it might exert an agonist (or partial agonist) effect at alpha(2)-adrenergic receptors or interact at alpha(2)-adrenergic heteroreceptors. Drug discrimination studies in rats indicate that TDIQ: (1) serves as a discriminative stimulus, (2) may be useful in the treatment of symptoms associated with the abuse of cocaine, and (3) exhibits a low potential for abuse. In addition, TDIQ exhibits a dose-dependent and wide dissociation between doses that produce an anxiolytic-like effect or an inhibition of "snack" consumption in mice and doses that produce minimal, if any, effects in tests that measure a potential for disruption of coordinated movement or motor activity. Also, TDIQ displays negligible effects on the heart rate (HR) and blood pressure (BP) of mice. Taken together, the preclinical data suggest that TDIQ exhibits a favorable ratio of therapeutic-like effects (anxiolytic, therapeutic adjunct in the treatment of cocaine abuse, and appetite suppression) to side effect-like activities (behavioral impairment, drug abuse, or adverse cardiovascular effect). As such, TDIQ could: (1) be a forerunner for a new type of chemical entity in the treatment of certain forms of anxiety and/or obesity and (2) serve as a structural template in the discovery and development of additional agents that might be selective for alpha(2)-adrenergic receptors.
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PMID:TDIQ (5,6,7,8-tetrahydro-1,3-dioxolo [4,5-g]isoquinoline): discovery, pharmacological effects, and therapeutic potential. 1807 26

Deficits in dopamine D2/D3 receptor (D2R/D3R) binding availability using PET imaging have been reported in obese humans and rodents. Similar deficits have been reported in cocaine-addicts and cocaine-exposed primates. We found that D2R/D3R binding availability negatively correlated with measures of body weight at the time of scan (ventral striatum), at 1 (ventral striatum) and 2 months (dorsal and ventral striatum) post scan in rats. Cocaine preference was negatively correlated with D2R/D3R binding availability 2 months (ventral striatum) post scan. Our findings suggest that inherent deficits in striatal D2R/D3R signaling are related to obesity and drug addiction susceptibility and that ventral and dorsal striatum serve dissociable roles in maintaining weight gain and cocaine preference. Measuring D2R/D3R binding availability provides a way for assessing susceptibility to weight gain and cocaine abuse in rodents and given the translational nature of PET imaging, potentially primates and humans.
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PMID:PET imaging predicts future body weight and cocaine preference. 2188 93

Obesity is a cause of sleep breathing disorders that result in excessive daytime sleepiness. We describe the adaptive strategy used by an obese person who started to snort cocaine to remedy incoercible drowsiness affecting his working financial skills. Clinical workup documented severe sleep apnea, which was treated by noninvasive ventilation and resulted in withdrawing cocaine abuse. Undiagnosed sleep disorders may trigger surreptitious psychostimulant abuse in vulnerable individuals.
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PMID:Cocaine abuse and sleep apnea in severe obesity. 2351 53

Loss of control over hedonically motivated actions is a defining component of impulse control disorders, such as drug dependence and the proposed 'food addiction' model of obesity. Devolution from goal-directed to compulsively maintained behaviors is partially attributed to abnormalities in the orbitofrontal cortex, an area critical in reward valuation. In the current study, overlapping reductions in orbitofrontal gray matter volume relating to body mass index were seen in healthy control and cocaine-dependent individuals, as well as in relation to duration of cocaine abuse, providing support for a shared neuropathology between the two conditions potentially related to dysfunctional reward-seeking behavior.
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PMID:Overlapping decline in orbitofrontal gray matter volume related to cocaine use and body mass index. 2392 55

Septo-Optic Dysplasia (SOD) is a rare disorder with postulated genetic and environmental etiology. Whilst initially considered as a very rare disease (defined as incidence of approx. 1 in 50,000 births) recent data gave a reported incidence of 1 in 10,000, with equal sex distribution. The diagnosis of SOD is predominantly a clinical one, and made with the presence of two or more features of the classic triad: 1) hypopituitarism, 2) optic nerve hypoplasia, and 3) midline brain defects, typically absence or hypoplasia of the septum pellucidum and/or corpus callosum. Hypopituitarism ranges from isolated to multiple hormone deficits, with diabetes insipidus in a minority. The condition is heterogeneous and may also manifest additional brain defects. Although homozygous mutations in the homeobox gene HESX1 have been identified in SOD, these are uncommon and genetic diagnosis can be made in only <1% of patients with autosomal recessive inheritance. Autosomal dominant inheritance has also been reported. SOX2, SOX3 and OTX2 mutations have also been identified in some forms of SOD. The aetiology of SOD is uncertain but viral infections, environmental teratogens and vascular or degenerative damage have been postulated to account for its sporadic occurrence. Other factors (endogenous or exogenous) include parental age, parity, smoking, alcohol and substance abuse, antenatal bleeding, and ethnicity. Cocaine abuse during pregnancy, which is a potent vasoconstrictor has recently been identified as a potential external cause. The phenotype of SOD is highly variable; the clinical picture may include visual impairment, short stature, obesity and sleep-wake inversion. Approximately 75-80% of patients exhibit optic nerve hypoplasia, which may be the first presenting feature. Pituitary insufficiency may evolve over time, and children with possible SOD must be kept under careful endocrine follow-up. Untreated hormonal abnormalities will further jeopardize neurodevelopment of children with SOD and could also lead to life-threatening adrenal crises. The attention should be focussed on early diagnosis and treatment and education of paediatricians how to recognize this complex disorder.
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PMID:New insights into septo-optic dysplasia. 2480 13

Cocaine abuse and obesity are serious public health problems, and studies suggest that both dopamine and serotonin systems are involved in regulating the consumption of drugs and food. Lorcaserin has serotonin (5-HT)2C receptor agonist actions, is approved by the U.S. Food and Drug Administration for treating obesity, and might be effective for treating cocaine abuse. These studies characterized the pharmacokinetic and behavioral profiles of lorcaserin (intragastric administration) and determined the effectiveness of lorcaserin to alter discriminative stimulus and reinforcing effects of cocaine (intravenous administration) in rhesus monkeys. Administered acutely, lorcaserin dose-dependently increased the occurrence of yawning while decreasing spontaneous activity and operant responding for food. These effects appeared within 30-60 minutes of administration and began to dissipate by 240 minutes, a time course closely matching plasma concentrations of lorcaserin. In monkeys discriminating cocaine from saline, lorcaserin alone did not occasion cocaine-appropriate responding but shifted the cocaine dose-response curve to the right and down in two of three monkeys. When administered acutely, lorcaserin dose-dependently decreased the rate at which monkeys responded for infusions of cocaine. When administered chronically, 3.2 mg/kg lorcaserin reduced the rate of cocaine-maintained responding by 50% for the duration of a 14-day treatment period. Together, these results show that lorcaserin attenuates the discriminative stimulus effects of cocaine after acute administration and the reinforcing effects of cocaine after acute and repeated administration, consistent with the view that it might have utility in treating cocaine abuse.
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PMID:Lorcaserin Reduces the Discriminative Stimulus and Reinforcing Effects of Cocaine in Rhesus Monkeys. 2653 42