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1.
Cureus ; 13(2): e13434, 2021 Feb 18.
Article de Anglais | MEDLINE | ID: mdl-33758719

RÉSUMÉ

Although data on the prevalence of anticholinergic misuse is scarce, it has been reported among psychiatric patients. Anticholinergic drugs can act as potent indirect dopamine agonists in the limbic system, a mechanism that has been hypothesized to explain their misuse potential among patients. In psychiatric practice settings, the use of typical antipsychotics in conjunction with anticholinergics is common, with the latter mainly used to manage extrapyramidal side effects of the former. Haloperidol is a first-generation (typical) antipsychotic with weak anticholinergic properties that may sometimes be potentiated when it is used in combination with other anticholinergic medications. This combination can induce significant gastrointestinal hypomotility, constipation, and rarely even paralytic ileus. We present the case of a 67-year-old African American male with a history of schizophrenia, benign prostatic hyperplasia, and essential hypertension, who abruptly started misusing benztropine, without any prior history of a substance use disorder. This case highlights the importance of obtaining a detailed history when previously stable psychiatric patients develop acute physical symptoms. It also illustrates the importance of care coordination among care providers and the central role of the psychiatrist in the care of patients with medical comorbidities.

2.
Eur J Pharmacol ; 880: 173175, 2020 Aug 05.
Article de Anglais | MEDLINE | ID: mdl-32416183

RÉSUMÉ

There are no medications that target the neurotoxic effects or reduce the use of methamphetamine. Recombinant T-cell receptor ligand (RTL) 1000 [a partial major histocompatibility complex (pMHC) class II construct with a tethered myelin peptide], addresses the neuroimmune effects of methamphetamine addiction by competitively inhibiting the disease-promoting activity of macrophage migration inhibitory factor to CD74, a key pathway involved in several chronic inflammatory conditions, including substance use disorders. We previously reported that RTL constructs improve learning and memory impairments and central nervous system (CNS) inflammation induced by methamphetamine in mouse models. The present study in Lewis rats evaluated the effects of RTL1000 on maintenance of self-administration and cue-induced reinstatement using operant behavioral methods. Post-mortem brain and serum samples were evaluated for the levels of inflammatory factors. Rats treated with RTL1000 displayed significantly fewer presses on the active lever as compared to rats treated with vehicle during the initial extinction session, indicating more rapid extinction in the presence of RTL1000. Immunoblotting of rat brain sections revealed reduced levels of the pro-inflammatory chemokine (C-C motif) ligand 2 (CCL2) in the frontal cortex of rats treated with RTL1000, as compared to vehicle. Post hoc analysis identified a positive association between the levels of CCL2 detected in the frontal cortex and the number of lever presses during the first extinction session. Taken together, results suggest that RTL1000 may block downstream inflammatory effects of methamphetamine exposure and facilitate reduced drug seeking-potentially offering a new strategy for the treatment of methamphetamine-induced CNS injury and neuropsychiatric impairments.


Sujet(s)
Stimulants du système nerveux central/effets indésirables , Comportement de recherche de substances/effets des médicaments et des substances chimiques , Troubles de la mémoire/traitement médicamenteux , Métamfétamine/effets indésirables , Neuroprotecteurs/usage thérapeutique , Protéines de fusion recombinantes/usage thérapeutique , Troubles liés à une substance/traitement médicamenteux , Animaux , Comportement animal/effets des médicaments et des substances chimiques , Encéphale/effets des médicaments et des substances chimiques , Encéphale/métabolisme , Chimiokine CCL2/métabolisme , Modèles animaux de maladie humaine , Extinction (psychologie)/effets des médicaments et des substances chimiques , Immunothérapie , Mâle , Troubles de la mémoire/induit chimiquement , Rats de lignée LEW , Autoadministration
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