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Amphetamine calcium channels

Přemysl Mladěnka, Lenka Applová, Jiří Patočka, Vera Marisa Costa, Fernando Remiao, Jana Pourová, Aleš Mladěnka, Jana Karlíčková, Luděk Jahodář, Marie Vopršalová, Kurt J Varner, Martin Štěrba
Cardiovascular diseases are a leading cause of morbidity and mortality in most developed countries of the world. Pharmaceuticals, illicit drugs, and toxins can significantly contribute to the overall cardiovascular burden and thus deserve attention. The present article is a systematic overview of drugs that may induce distinct cardiovascular toxicity. The compounds are classified into agents that have significant effects on the heart, blood vessels, or both. The mechanism(s) of toxic action are discussed and treatment modalities are briefly mentioned in relevant cases...
January 5, 2018: Medicinal Research Reviews
Xincai Ji, Sucharita Saha, Guangping Gao, Amy W Lasek, Gregg E Homanics, Melissa Guildford, Andrew R Tapper, Gilles E Martin
Voltage-gated sodium channels are essential for generating the initial rapid depolarization of neuronal membrane potential during action potentials (APs) that enable cell-to-cell communication, the propagation of signals throughout the brain, and the induction of synaptic plasticity. Although all brain neurons express one or several variants coding for the core pore-forming sodium channel α subunit, the expression of the β (β1-4) auxiliary subunits varies greatly. Of particular interest is the β4 subunit, encoded by the Scn4b gene, that is highly expressed in dorsal and ventral (i...
2017: Frontiers in Cellular Neuroscience
L Hondebrink, A H A Verboven, W S Drega, S Schmeink, M W G D M de Groot, R G D M van Kleef, F M J Wijnolts, A de Groot, J Meulenbelt, R H S Westerink
Annual prevalence of the use of common illicit drugs and new psychoactive substances (NPS) is high, despite the often limited knowledge on the health risks of these substances. Recently, cortical cultures grown on multi-well microelectrode arrays (mwMEAs) have been used for neurotoxicity screening of chemicals, pharmaceuticals, and toxins with a high sensitivity and specificity. However, the use of mwMEAs to investigate the effects of illicit drugs on neuronal activity is largely unexplored. We therefore first characterised the cortical cultures using immunocytochemistry and show the presence of astrocytes, glutamatergic and GABAergic neurons...
July 2016: Neurotoxicology
Krasnodara N Cameron, Ernesto Solis, Iwona Ruchala, Louis J De Felice, Jose M Eltit
Amphetamine (AMPH) and its more potent enantiomer S(+)AMPH are psychostimulants used therapeutically to treat attention deficit hyperactivity disorder and have significant abuse liability. AMPH is a dopamine transporter (DAT) substrate that inhibits dopamine (DA) uptake and is implicated in DA release. Furthermore, AMPH activates ionic currents through DAT that modify cell excitability presumably by modulating voltage-gated channel activity. Indeed, several studies suggest that monoamine transporter-induced depolarization opens voltage-gated Ca(2+) channels (CaV), which would constitute an additional AMPH mechanism of action...
November 2015: Cell Calcium
John R Richards, Timothy E Albertson, Robert W Derlet, Richard A Lange, Kent R Olson, B Zane Horowitz
BACKGROUND: Overdose of amphetamine, related derivatives, and analogues (ARDA) continues to be a serious worldwide health problem. Patients frequently present to the hospital and require treatment for agitation, psychosis, and hyperadrenegic symptoms leading to pathologic sequelae and mortality. OBJECTIVE: To review the pharmacologic treatment of agitation, psychosis, and the hyperadrenergic state resulting from ARDA toxicity. METHODS: MEDLINE, PsycINFO, and the Cochrane Library were searched from inception to September 2014...
May 1, 2015: Drug and Alcohol Dependence
Bing-Hsuan Lei, Jyh-Horng Chen, Hsiang-Shu Yin
Manganese-enhanced magnetic resonance imaging (MEMRI) has been extensively used in studying the structural and functional features of the central nervous system (CNS). Divalent manganese ion (Mn(2+)) not only enhances MRI contrast, but also enters cells via voltage-gated calcium channels or ionotropic glutamate receptors, which represents an index of neural activities. In the current mouse model, following the repeated amphetamine (Amph) treatment, a reduction of reactivity to thermal pain stimulus was noticed...
November 7, 2014: Neuroscience Letters
Stefan M Berger, Dusan Bartsch
The use of specific activators and inhibitors that penetrate the central nervous system has suggested an essential functional role of L-type calcium channels (LTCC) in several important physiological processes of the brain, including the modulation of the mesoaccumbal dopamine signalling pathway, synaptic transmission of auditory stimuli and synaptic plasticity of neutral and aversive learning and memory processes. However, the lack of selectivity of available pharmacological agents towards the most prominent LTCC isoforms in the brain, namely Cav1...
August 2014: Cell and Tissue Research
Grażyna Biała, Piotr Polak, Agnieszka Michalak, Marta Kruk-Słomka, Barbara Budzyńska
BACKGROUND: Nonsomatic signs of psychostimulant withdrawal, difficult to demonstrate in animal paradigms, may appear to promote drug seeking and drug relapse in humans; thus, it is important to understand the mechanisms that mediate this kind of behaviors. The present study was undertaken to examine the calcium-dependent mechanism of negative nonsomatic and anhedonia-related symptoms of acute and protracted withdrawal of nicotine and D-amphetamine. METHODS: Mice were chronically treated with nicotine (seven days, three times daily, 3...
April 2014: Pharmacological Reports: PR
Giuseppe Gangarossa, Sophie Laffray, Emmanuel Bourinet, Emmanuel Valjent
The fine-tuning of neuronal excitability relies on a tight control of Ca(2+) homeostasis. The low voltage-activated (LVA) T-type calcium channels (Cav3.1, Cav3.2 and Cav3.3 isoforms) play a critical role in regulating these processes. Despite their wide expression throughout the central nervous system, the implication of T-type Cav3.2 isoform in brain functions is still poorly characterized. Here, we investigate the effect of genetic ablation of this isoform in affective disorders, including anxiety, cognitive functions as well as sensitivity to drugs of abuse...
2014: Frontiers in Behavioral Neuroscience
Robin M Voigt, Jennifer L Riddle, T Celeste Napier
RATIONALE: Fendiline is a GABAB receptor-positive allosteric modulator and L-type Ca²⁺ channel blocker that is safe for human use. Based on these pharmacological properties, fendiline may be useful to disrupt associative memories that can drive relapse to drug use in drug-addicted individuals OBJECTIVE: The current study evaluated the potential of fendiline to inhibit the maintenance and expression of learned associations between methamphetamine (meth) and an environmental context using conditioned place preference (CPP) in rats, to model for the associative learning that occurs during drug abuse by humans METHODS: Following meth conditioning (1 mg/kg), fendiline (5 mg/kg) was administered at various post-conditioning times to ascertain if there was a temporal window during which fendiline would be effective...
May 2014: Psychopharmacology
Ya-Jean Wang, Ming-Huan Chan, Hwei-Hisen Chen
Methamphetamine (MA), a highly abused amphetamine-like psychostimulant, has surged in popularity worldwide in the last decade. Repeated MA exposure has been shown to affect the alternative splice variant expression of large conductance Ca(2+)-activated K(+) (BK) channels. It remains unclear whether MA affects BK channel activity. The present study investigated the effects of MA on BK channels in NG108-15 mouse neuroblastoma×rat glioma hybrid cells using whole-cell and cell-attached patch clamp techniques. In whole-cell recordings, the macroscopic K(+) outward currents were inhibited by MA with an EC50 of 146μM, but not affected by dopamine (DA)...
November 25, 2013: Toxicology Letters
Anindya Bhattacharya, Qi Wang, Hong Ao, James R Shoblock, Brian Lord, Leah Aluisio, Ian Fraser, Diane Nepomuceno, Robert A Neff, Natalie Welty, Timothy W Lovenberg, Pascal Bonaventure, Alan D Wickenden, Michael A Letavic
BACKGROUND AND PURPOSE: An increasing body of evidence suggests that the purinergic receptor P2X, ligand-gated ion channel, 7 (P2X7) in the CNS may play a key role in neuropsychiatry, neurodegeneration and chronic pain. In this study, we characterized JNJ-47965567, a centrally permeable, high-affinity, selective P2X7 antagonist. EXPERIMENTAL APPROACH: We have used a combination of in vitro assays (calcium flux, radioligand binding, electrophysiology, IL-1β release) in both recombinant and native systems...
October 2013: British Journal of Pharmacology
Nicholas I Cilz, Lalitha Kurada, Binqi Hu, Saobo Lei
Whereas the entorhinal cortex (EC) receives profuse dopaminergic innervations from the midbrain, the effects of dopamine (DA) on γ-Aminobutyric acid (GABA)ergic interneurons in this brain region have not been determined. We probed the actions of DA on GABAA receptor-mediated synaptic transmission in the EC. Application of DA increased the frequency, not the amplitude, of spontaneous IPSCs (sIPSCs) and miniature IPSCs (mIPSCs) recorded from entorhinal principal neurons, but slightly reduced the amplitude of the evoked IPSCs...
December 2014: Cerebral Cortex
Eduardo Kenji Hamasato, Ana Paula Ligeiro de Oliveira, Adriana Lino-dos-Santos-Franco, Alison Ribeiro, Viviane Ferraz de Paula, Jean Pierre Schatzmann Peron, Amílcar Sabino Damazo, Wothan Tavares-de-Lima, João Palermo-Neto
Glutamate acts as a neurotransmitter within the Central Nervous System (CNS) and modifies immune cell activity. In lymphocytes, NMDA glutamate receptors regulate intracellular calcium, the production of reactive oxygen species and cytokine synthesis. MK-801, a NMDA receptor open-channel blocker, inhibits calcium entry into mast cells, thereby preventing mast cell degranulation. Several lines of evidence have shown the involvement of NMDA glutamate receptors in amphetamine (AMPH)-induced effects. AMPH treatment has been reported to modify allergic lung inflammation...
August 2013: International Immunopharmacology
T A Roepke, A W Smith, O K Rønnekleiv, M J Kelly
Hypothalamic proopiomelanocortin (POMC) neurons are controlled by many central signals, including serotonin. Serotonin increases POMC activity and reduces feeding behavior via serotonion [5-hydroxytryptamine (5-HT)] receptors by modulating K(+) currents. A potential K(+) current is the M-current, a noninactivating, subthreshold outward K(+) current. Previously, we found that M-current activity was highly reduced in fasted vs. fed states in neuropeptide Y neurons. Because POMC neurons also respond to energy states, we hypothesized that fasting may alter the M-current and/or its modulation by serotonergic input to POMC neurons...
June 1, 2012: American Journal of Physiology. Endocrinology and Metabolism
S Umukoro, T O Bakre, C Onwuchekwa
Calcium channel blockers (CCBs) are widely used as therapeutic agents, for the treatment of cardiovascular disorders. However, the discovery that CCBs bind to various regions of the brain suggest that they might also offer some beneficial effects in the treatment of neuropsychiatry disorders. This study was carried out to evaluate the anti-psychotic and sedative effects of two notable calcium channel blockers, verapamil and nifedipine in mice. The anti-psychotic effects of the CCBs were studied in the animal model of amphetamine-induced stereotyped behavioral disorders...
December 2010: African Journal of Medicine and Medical Sciences
Xavier Wittebole, Philippe Hantson
INTRODUCTION: There is an increasing interest in recent developments in bioartificial and non-bioartificial devices, so called extracorporeal liver assist devices, which are now used widely not only to increase drug elimination, but also to enhance the removal of endogenous substances in acute liver failure. Most of the non-bioartificial techniques are based on the principle of albumin dialysis. The objective is to remove albumin-bound substances that could play a role in the pathophysiology of acute liver failure by dialysing blood against an albumin-containing solution across a high flux permeable membrane...
November 2011: Clinical Toxicology
Vincent Leviel
Spontaneous and/or stimulated neural activity of the nigrostriatal dopamine (DA) pathway makes amines run out from the neurons. This DA dynamic follows a rather complex path, running in or out the terminals, and flushing or diffusing into the extracellular space. The location of this leakage is not limited to the axon terminals; it also occurs from the cell bodies and dendrites. This molecular release mechanism was, for a long time, considered as being produced, in part, by the exocytosis of previously stored vesicles...
August 2011: Journal of Neurochemistry
Thomas P Giordano, Thomas F Tropea, Shirish S Satpute, Martina J Sinnegger-Brauns, Joerg Striessnig, Barry E Kosofsky, Anjali M Rajadhyaksha
L-type Ca(2+) channel (LTCC)-activated signaling cascades contribute significantly to psychostimulant-induced locomotor sensitization; however, the precise contribution of the two brain-specific subunits Ca(v)1.2 and Ca(v)1.3 remains mostly unknown. In this study, by using amphetamine and cocaine locomotor sensitization in mutant mice expressing dihydropyridine (DHP)-insensitive Ca(v)1.2 LTCCs (Ca(v)1.2DHP(-/-)), we find that, as opposed to a previously identified role of the Ca(v)1.3 subunit of LTCCs in development of sensitization, the Ca(v)1...
December 15, 2010: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jason M Uslaner, Sean M Smith, Sarah L Huszar, Rashida Pachmerhiwala, Richard M Hinchliffe, Joshua D Vardigan, Shannon J Nguyen, Nathan O Surles, Lihang Yao, James C Barrow, Victor N Uebele, John J Renger, Janet Clark, Pete H Hutson
T-type calcium channels are important in burst firing and expressed in brain regions implicated in schizophrenia. Therefore, we examined the effects of novel selective T-type calcium channel antagonists in preclinical assays predictive of antipsychotic-like activity. TTA-A2 blocked the psychostimulant effects of amphetamine and MK-801 and decreased conditioned avoidance responding. These effects appeared mechanism based, rather than compound specific, as two structurally dissimilar T-type antagonists also reduced amphetamine-induced psychomotor activity...
March 2012: Neuropharmacology
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