Browsing by Subject "Cocaine"
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Item ANTI NEUTROPHIL CYTOPLASMIC ANTIBODY POSITIVE VASCULITIS ASSOCIATED WITH LEVAMISOLE CONTAMINATION IN STREET DRUGS(2013-04-12) White, LeonPurpose: The antihelminth drug, Levamisole is widely used to cut cocaine and has been reported to cause aganulocytosis and neutropenia. It can present with an elvated perinuclear antineutrophil cytoplasmic antibody (P-ANCA), anti-nuclear antibody (ANA), myeloperoxidase (MPO), and proteinase 3 (PR3). The purpose of this communication is to demonstrate potential rheumatological side effect of cocaine use related to levamisole contamination. Methods: We present 2 cases of P-ANCA positive vasculitis in patients with heavy use of cocaine. The pertinent social history, clinical findings and laboratory data were obtained from electronic medical records by authorized physicians. A PubMed search was performed using the terms levamisole and vasculitis, cocaine and levamisole, cocaine and vasculitis, and vasculitis. Articles and cases published within the last 10 years were considered. For the epidemiological statistics, we included data reported by the National Institute on Drug Abuse (NIDA), National Survey on Drug Use and Health (NSDUH), the Center for Disease Control and Prevention (CDC) and United States Drug Enforcement Agency (DEA). Results: Two patients seen in the JPS presented with painful, purpuric skin lesions on their ears, arms, forearms and face. Laboratory assays reveal neutropenia, with a positive ANA and P-ANA. Conclusions: These cases highlight the diagnostic criteria of levamisole induced vasculitis based on the presence of neutropenia, necrotizing vasculitis, rhematological findings, social history, the lack of organ involvement and the location of the lesions. Levamisole vasculitis should be clinically distinguished from other systemic disorders such as Lupus, Wegener's granulomatosis, Churgg-Strauss, and Microscopic polyangiitis.Item Locomotor and discriminative stimulus effects of three benzofuran compounds in comparison to abused psychostimulants(Elsevier B.V., 2023-08-21) Hill, Rebecca D.; Shetty, Ritu A.; Sumien, Nathalie; Forster, Michael J.; Gatch, Michael B.AIMS: Benzofurans are used recreationally, due their ability to cause psychostimulant and/or entactogenic effects, but unfortunately produce substantial adverse effects, including death. Three benzofurans 5-(2-aminopropyl)-2,3-dihydrobenzofuran (5-APDB), 5-(2-aminopropyl)-2,3-dihydrobenzofuran (5-MAPB) and 6-(2-aminopropyl) benzofuran (6-APB) were tested to determine their behavioral effects in comparison with 2,3-methylenedioxymethamphetamine (MDMA), cocaine, and methamphetamine. METHODS: Locomotor activity was tested in groups of 8 male Swiss-Webster mice in an open-field task to screen for locomotor stimulant or depressant effects and to identify behaviorally active doses and times of peak effect. Discriminative stimulus effects were tested in groups of 6 male Sprague-Dawley rats trained to discriminate MDMA (1.5 mg/kg), cocaine (10 mg/kg), or methamphetamine (1 mg/kg) from saline using a FR 10 for food in a two-lever operant task. RESULTS: In the locomotor activity test, MDMA (ED(50) = 8.34 mg/kg) produced peak stimulant effects 60 to 80 min following injection. 5-MAPB (ED(50) = 0.92 mg/kg) produced modest stimulant effects 50 to 80 min after injection, whereas 6-APB (ED(50) = 1.96 mg/kg) produced a robust stimulant effect 20 to 50 min after injection. 5-APDB produced an early depressant phase (ED(50) = 3.38 mg/kg) followed by a modest stimulant phase (ED(50) = 2.57 mg/kg) 20 to 50 min after injection. In the drug discrimination tests, 5-APDB (ED(50) = 1.02 mg/kg), 5-MAPB (ED(50) = 1.00 mg/kg) and 6-APB (ED(50) = 0.32 mg/kg) fully substituted in MDMA-trained rats, whereas only 5-MAPB fully substituted for cocaine, and no compounds fully substituted for methamphetamine. CONCLUSIONS: The synthetic benzofuran compound 5-APDB and 5-MAPB produced weak locomotor effects, whereas 6-APB produced robust locomotor stimulant effects. All compounds were more potent than MDMA. All three compounds fully substituted in MDMA-trained rats suggesting similar subjective effects. Taken together, these results suggest that these benzofuran compounds may have abuse liability as substitutes for MDMA.Item The Involvement of D1 and D2 Dopamine Receptors in Cocaine Self-Administration(1996-06-01) Peltier, Rachel; Michael Forster; Patricia A. Gwirtz; Thomas YorioPeltier, Rachel L., The Involvement of D1 and D2 Dopamine Receptors in Cocaine Self-Administration. Doctor of Philosophy (Biomedical Sciences), June 1996, 195 pp. introduction, 6 chapters, discussion, bibliography, 91 titles. D1 and D2 dopamine receptor subtypes have been implicated in producing the reinforcing properties of cocaine. Chronic exposure to cocaine produces tolerance to its reinforcing effects in rats trained to self-administer cocaine. The time between cocaine reinforcers (ISRT) is directly related to dose. A three-point dose-response curve (0.125, 0.25 and 0.5 mg/inj) for cocaine self-administration is obtained during a single test session, allowing determination of optimal tolerance effects of cocaine (20 mg/kg/8 hr/7 days; IP) as demonstrated by a shift of the curve to the right. To test if pharmacokinetic factors contribute to the development of tolerance to the reinforcing properties of cocaine (20 mg/kg/8hr/7days; IP), cocaine and benzoylecgonine (metabolite) were measured in the plasma and brains of rats given a challenge injection of cocaine (2.0 mg/kg; I.V.). Chronic cocaine did not reduce the concentration of cocaine must be due to pharmacodynamics changes. Acute pretreatment with either the direct dopamine agonists d-amphetamine (0.32-3.2 mg/kg) or methamphetamine (1.0 mg/kg) did not consistently change cocaine self-administration. Chronic high-dose treatment with d-amphetamine and methamphetamine produced cross-tolerance to the reinforcing effects of cocaine but apomorphine (0.32-3.2 mg/kg) did not. In contrast, acute pretreatment with dopamine antagonists; flupentixol (mixed D1 and D2, 0.032-1.0 mg/kg), SCH23390 (specific D1, 0.0032-0.32 mg/kg), or eticlopride (specific D2, 0.0032 -3.2 mg/kg); dose-dependently decreased the reinforcing effects of cocaine (ISRT). Chronic treatment with mixed of D1 antagonists (flupentixol, 3.2 mg/kg/12 hr/5 days; or SCH23390, 0.25 mg/kg/12 hr/7 days) produced sensitization to the reinforcing effects of cocaine, but the D2 antagonist eticlopride (0.25 mg/kg/12 hr/7 days) produced cross-tolerance to the reinforcing effects of cocaine. In summary, both the D1 and D2 receptor subtypes seem to be involved in the acute effects of cocaine; however, the development of tolerance to cocaine appears to involve only the D1 receptor subtype.