Yasco Aracava's research while affiliated with Loyola University Maryland and other places

... Na Guerra do Golfo, ocorrida no início da década de 1990, os militares dos Estados Unidos da América utilizaram o brometo de piridostigmina como pré-tratamento para uma eventual exposição ao Soman. Apesar da sua utilização no supracitado conflito, foi somente em 2003 que o brometo de piridostigmina foi aprovado pelo governo dos Estados Unidos da América para ser utilizado como pré-tratamento por militares (Pereira et al. 2008). ...

... In toxicology studies, significant changes in body and organ weight are usually regarded as the most intuitive indicators for evaluating toxic chemicals [60]. Moreover, previous studies have shown that the primary toxic effect of CHP is neurological toxicity [55,61,62]. AChE activity was significantly inhibited in the CHP-treated group in our experiments, which may lead to structural defects in the digestive tract [32]. ...

... The galanthamine dose of 10 mg/kg assured 100% survival of guinea pigs and decreased seizure duration. Galanthamine as a pretreatment against soman exposure was further investigated in Cynomolgus monkeys (Lane et al., 2020). It was shown in this study that animals orally pretreated with galanthamine (3.0 mg/kg), challenged with supralethal doses of soman (4xLD50) and post-treated with conventional antidotes atropine (0.4 mg/kg), pralidoxime (30 mg/kg), and midazolam (0.32 mg/kg), survived within 24 hours after intoxication. ...

... Preclinical studies have indicated that HNKs display antidepressant-like activity in rodent models of anxiety/depression [125]. However, the pharmacological properties of (2R,6R)-HNK and its contribution to the actions of (R,S)-ketamine are still up for debate [128][129][130][131][132][133]. We are waiting for the results of clinical trials regarding (2R,6R)-HNK and its potential therapeutic applications in TRD [131]. ...

... Recent work examined HNKs and their pharmacological relevance [81,82]. Most notably, (2R,6R)-HNK shows potential therapeutic efficacy at a dose that does not involve the direct inhibition of the NMDAR receptor [82][83][84] (see below). ...

... Phys and Proc blocked the open channels with rate constants of 6 ⅐ 10 6 M Ϫ1 s Ϫ1 and 2 ⅐ 10 6 M Ϫ1 s Ϫ1 , respectively, and unblocked with rates of 200 s Ϫ1 . The blocking rate constants were in the same range as those found by previous investigators (Adams 1977;Albuquerque et al. 1986;Neher and Steinbach 1978;Ogden et al. 1981). Ogden et al. (1981) reported an unblocking rate for benzocaine similar to that found by us, whereas Neher and Steinbach (1978) saw a rate of unblock for lidocaine derivatives of 2,300 s Ϫ1 , corresponding to the ''flickering block'' caused by these substances. ...

... These "nerve agents" represent a major threat to soldiers in battle fields and occasionally have been used by terrorists against civilians (Gunderson et al., 1992;Solberg and Belking, 1997). Although it has long been accepted that inhibition of cholinesterase is the mechanism underlying the toxic effects of OPs, these compounds have been shown to interact with molecular targets other than cholinesterases in the peripheral and central nervous systems (Idriss et al., 1986;Rao et al., 1987;Albuquerque et al., 1985Albuquerque et al., , 1987Albuquerque et al., , 1988Albuquerque et al., , 1994Rocha et al., 1992Rocha et al., , 1996c. Of particular interest is the report that at the neuromuscular junction VX increases acetylcholine (ACh) release by a mechanism unrelated to cholinesterase inhibition (Rao et al., 1987). ...

... Thus, the modulation of neuronal AChRs could lead to a cascade of synaptic events involving multiple neurotransmitters. Neuronal nicotinic AChRs are known to be an important target of various chemicals, including nicotine, carbachol, d-tubocurarine, alcohols, general anesthetics, some insecticides, heavy metals, and several natural toxins (Albuquerque et al., 1989Castro and Albuquerque, 1993;Ishihara et al., 1995;Mori et al., 2001;Nagata et al., 1996Nagata et al., , 1997aNagata et al., ,b, 1998aSwanson and Albuquerque, 1992). ...

... An enhancement of muscarinic cholinergic function by memantine was reported (Drever et al., 2007), but this was not supported by the result that memantine's LTP-enhancing effect was not blocked by scopolamine. Other than NMDA receptors, memantine has been shown to block a7 nicotinic receptors (Aracava et al., 2005) and 5-HT3 receptors (Rammes et al., 2001;Reiser et al., 1988). In addition, memantine increased the release of dopamine (Spanagel et al., 1994) and histamine (Motawaj et al., 2011) that may enhance hippocampal LTP in behaving rats (Luo and Leung, 2010). ...

... They also proved that a combination of galanthamine and atropine, as post-treatment administered 30 min after soman challenge, was successful in preventing lethality, compared to atropine alone or galanthamine alone. Galanthamine may also prevent the decline in hippocampal glutamatergic transmission in guinea pigs challenged with soman (1xLD 50 ) which is a possible mechanism of prevention of cognitive defects that develop long after acute exposure to nerve agents (Alexandrova et al., 2014). Another study (Hilmas et al., 2009) investigated galanthamine as an addition to post-therapy consisting of atropine and 2-PAM against VX in guinea pigs. ...