Gianluigi Tanda, Ph.D.

@article{Mereu2017,

title = {The unique psychostimulant profile of (+/-)-modafinil: investigation of behavioral and neurochemical effects in mice.},

author = {Maddalena Mereu and Lauren E Chun and Thomas E Prisinzano and Amy Hauck Newman and Jonathan L Katz and Gianluigi Tanda},

url = {https://www.ncbi.nlm.nih.gov/pubmed/27545285},

doi = {10.1111/ejn.13376},

issn = {1460-9568 (Electronic); 0953-816X (Linking)},

year  = {2017},

date = {2017-01-01},

journal = {Eur J Neurosci},

volume = {45},

number = {1},

pages = {167--174},

address = {Medication Development Program, Molecular Targets and Medications Discovery Branch, Department of Health and Human Services, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 333 Cassell Drive, Baltimore, MD, 21224, USA.},

abstract = {Blockade of dopamine (DA) reuptake via the dopamine transporter (DAT) is a primary mechanism identified as underlying the therapeutic actions of (+/-)-modafinil (modafinil) and its R-enantiomer, armodafinil. Herein, we explored the neurochemical and behavioral actions of modafinil to better characterize its psychostimulant profile. Swiss-Webster mice were implanted with microdialysis probes in the nucleus accumbens shell (NAS) or core (NAC) to evaluate changes in DA levels related to acute reinforcing actions of drugs of abuse. Additionally, subjective effects were studied in mice trained to discriminate 10 mg/kg cocaine (i.p.) from saline. Modafinil (17-300 mg/kg, i.p.) significantly increased NAS and NAC DA levels that at the highest doses reached ~300% at 1 h, and lasted > 6 h in duration. These elevated DA levels did not show statistically significant regional differences between the NAS and NAC. Modafinil produced cocaine-like subjective effects at 56-100 mg/kg when administered at 5 and 60 min before the start of the session, and enhanced cocaine effects when the two were administered in combination. Despite sharing subjective effects with cocaine, modafinil's psychostimulant profile was unique compared to that of cocaine and like compounds. Modafinil had lower potency and efficacy than cocaine in stimulating NAS DA. In addition, the cocaine-like subjective effects of modafinil were obtained at lower doses and earlier onset times than expected based on its dopaminergic effects. These studies suggest that although inhibition of DA reuptake may be a primary mechanism underlying modafinil's therapeutic actions, non DA-dependent actions may be playing a role in its psychostimulant profile.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Talbot2016,

title = {Rapid and sustained antidepressant properties of an NMDA antagonist/monoamine reuptake inhibitor identified via transporter-based virtual screening.},

author = {Jeffery N Talbot and Laura M Geffert and Jessica E Jorvig and Ruben I Goldstein and Cienna L Nielsen and Nicholas E Wolters and Mary Ellen Amos and Caitlin A Munro and Elizabeth Dallman and Maddalena Mereu and Gianluigi Tanda and Jonathan L Katz and Martin Indarte and Jeffry D Madura and Hailey Choi and Rehana K Leak and Christopher K Surratt},

url = {https://www.ncbi.nlm.nih.gov/pubmed/27569602},

doi = {10.1016/j.pbb.2016.08.007},

issn = {1873-5177 (Electronic); 0091-3057 (Linking)},

year  = {2016},

date = {2016-11-01},

journal = {Pharmacol Biochem Behav},

volume = {150-151},

pages = {22--30},

address = {Research Center on Substance Abuse and Depression, College of Pharmacy, Roseman University of Health Sciences, 11 Sunset Way, Henderson, NV 89014, USA. Electronic address: jtalbot@roseman.edu.},

abstract = {Rational design of lead compounds targeting monoamine transporters (MATs) is critical to developing novel therapeutics to treat psychiatric disorders including depression and substance abuse. A 3-D dopamine transporter (DAT) computer model was used to virtually screen a commercially available small molecule library for high DAT affinity drug-like compounds. One hit, coded "MI-4", inhibited human dopamine, norepinephrine, and serotonin transporters in vitro. In vivo administration in mice induced robust, dose-dependent antidepressant-like behaviors in learned helplessness models (tail suspension and forced swim tests). Moreover, chronic administration (21day, 10mg/kg, bid) reduced drinking latencies comparable to fluoxetine (10mg/kg, bid) in the novelty-induced hypophagia test, which requires chronic treatment to produce antidepressant-like effects. MI-4 (10mg/kg, bid) produced rapid (three-day) antidepressant-like effects in the social avoidance test following 10days of social defeat stress. Unlike ketamine, chronic administration of MI-4 increased social interaction scores while improving resiliency to the mood-altering effects of stress to over 70%. Importantly, MI-4 exhibited minimal abuse liability in behavioral and neurological models (conditioned place preference and dopamine in vivo microdialysis). MI-4 was found to be Ro-25-6981, an ifenprodil analog and reputed NMDA antagonist. The data suggest that Ro-25-6981, previously known for rapid-acting glutamatergic antidepressant actions, may also functionally inhibit monoamine reuptake and produces sustained antidepressant effects in vivo. This demonstrates, as proof of principle, the viability of combining these mechanisms to produce rapid and sustained antidepressant-like effects. Overall, these findings suggest MAT computational model-based virtual screening is a viable method for identifying antidepressant lead compounds of unique scaffold.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}