Tropisetron sensitizes α7 containing nicotinic receptors to low levels of acetylcholine in vitro and improves memory-related task performance in young and aged animals

Callahan, Patrick M.; Bertrand, Daniel; Bertrand, Sonia; Plagenhoef, Marc; Terry, Alvin V.

doi:10.1016/j.neuropharm.2017.02.025

Cited by 38 publications

(28 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In experimental studies, 5HT 3 R antagonism can reverse learning and memory deficits invoked by scopolamine or lesions to the cholinergic nucleus basalis of Meynert (Barnes et al, 1990;Chugh et al, 1991;Carli et al, 1997;Ohno and Watanabe, 1997). Antagonism at 5HT 3 R also improved novel object recognition in aged monkeys (Arnsten et al, 1997) and aged rats (Callahan et al, 2017). As previously discussed, 5-HT 3 Rs are highly expressed in the amygdala, hippocampus, and cortex, regions integral to memory processing (Gulyás et al, 1999;Walstab et al, 2010).…”

Section: Memory Disordersmentioning

confidence: 71%

“…Interestingly, tropisetron targets calcineurin as a central player in neuronal damage (Rahimian et al, 2011b) and, in keeping with the in vivo observation (Barzegar-Fallah et al, 2014), the inhibition of calcineurin phosphatase activity by tropisetron represents one plausible mode of action underlying the neuroprotective effects of this drug. Other mechanisms that potentially contribute to setrons' protection against vincristine-associated neuropathy could include their ability to activate a7 nAChR (Swartz et al, 2013;Fakhfouri et al, 2015;Callahan et al, 2017), induction of the anti-inflammatory transcriptional factor nuclear factor erythroid 2-related factor 2 and its downstream molecules heme oxygenase and catalase (Khalifeh et al, 2015), as well as inhibition of p38 MAPK (Liu et al, 2012;Stratz et al, 2012). Interventions that exert these effects have been shown to attenuate vincristineinduced neuropathy (Shen et al, 2015).…”

Section: B Neurotoxicity Associated With Cancer Chemotherapy Drugsmentioning

confidence: 99%

“…Activation of a7 nAChR is another mode of action for memory-boosting properties of tropisetron (Callahan et al, 2017). This receptor has received considerable attention as a potential therapeutic target in AD and schizophrenia (for review, see Bertrand et al, 2015).…”

Section: Memory Disordersmentioning

confidence: 99%

See 2 more Smart Citations

5-HT₃Receptor Antagonists in Neurologic and Neuropsychiatric Disorders: The Iceberg Still Lies beneath the Surface

et al. 2019

View full text Add to dashboard Cite

HT 3 receptor antagonists, first introduced to the market in the mid-1980s, are proven efficient agents to counteract chemotherapy-induced emesis. Nonetheless, recent investigations have shed light on unappreciated dimensions of this class of compounds in conditions with an immunoinflammatory component as well as in neurologic and psychiatric disorders. The promising findings from multiple studies have unveiled several beneficial effects of these compounds in multiple sclerosis, stroke, Alzheimer disease, and Parkinson disease. Reports continue to uncover important roles for 5-HT 3 receptors in the physiopathology of neuropsychiatric disorders, including depression, anxiety, drug abuse, and schizophrenia. This review addresses the potential of 5-HT 3 receptor antagonists in neurology-and neuropsychiatry-related disorders. The broad therapeutic window and high compliance observed with these agents position them as suitable prototypes for the development of novel pharmacotherapeutics with higher efficacy and fewer adverse effects.

show abstract

Section: Memory Disordersmentioning

confidence: 71%

Section: B Neurotoxicity Associated With Cancer Chemotherapy Drugsmentioning

confidence: 99%

See 1 more Smart Citation

5-HT₃Receptor Antagonists in Neurologic and Neuropsychiatric Disorders: The Iceberg Still Lies beneath the Surface

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In some initial clinical studies, tropisetron was also shown to improve auditory sensory gating (P50) deficits, cognitive impairments and negative symptoms in patients with schizophrenia [46, 47, 48]. We also recently observed robust cognitive enhancing effects of tropisetron in both young and aged rats in an NOR task as well as in aged male and female monkeys in a delayed match to sample, working/short-term memory task [30]. In sum, the fact that tropisetron can exert pro-cognitive effects in cases where α7 nAChRs are likely decreased (e.g., after chronic APD treatment in rodents as we have observed and in schizophrenia patients, who have commonly been exposed to APDs chronically) is particularly encouraging from an adjunctive treatment standpoint.…”

Section: Discussionmentioning

confidence: 99%

“…The NOR task was adapted from Ennaceur and Delacour [28] as we have published previously [29, 30]. Briefly, test subjects were acclimated to laboratory conditions (i.e., tail marking, daily handling, and weighing) for at least 3 days prior to experimentation.…”

Section: Methodsmentioning

confidence: 99%

Tropisetron enhances recognition memory in rats chronically treated with risperidone or quetiapine

Poddar

Callahan

Hernandez

et al. 2018

Biochemical Pharmacology

Self Cite

View full text Add to dashboard Cite

While impairments of cognition in schizophrenia have the greatest impact on long-term functional outcome, the currently prescribed treatments, antipsychotic drugs (APDs), do not effectively improve cognition. Moreover, while more than 20 years have been devoted to the development of new drugs to treat cognitive deficits in schizophrenia, none have been approved to date. One area that has not been given proper attention at the preclinical or clinical stage of drug development is the chronic medication history of the test subject. Hence, very little is known about how chronic treatment with drugs that affect multiple receptors like APDs influence the response to a potential pro-cognitive agent. Therefore, the purpose of this study was to evaluate the α7 nicotinic acetylcholine receptor (α7 nAChR) partial agonist, tropisetron in rats chronically treated with APDs with distinct pharmacological profiles. Rats were treated orally with either risperidone (2.5 mg/kg/day) or quetiapine (25.0 mg/kg/day) for 30 or 90 days and then an acute injection of vehicle or tropisetron (3.0 mg/kg) was administered before training in a novel object recognition (NOR) task. After a 48 h delay (when recollection of the familiar object was impaired in vehicle-treated animals) neither 30 nor 90 days of risperidone or quetiapine treatment improved NOR performance. In contrast, tropisetron markedly improved NOR performance in rats treated with either APD for 30 or 90 days. These animal data reinforce the argument that two commonly prescribed APDs are not pro-cognitive agents and that α7 nAChR ligands like tropisetron have potential as adjunctive treatments in schizophrenia.

show abstract

Effect of Tropisetron on Prevention of Emergence Delirium in Patients After Noncardiac Surgery

et al. 2020

View full text Add to dashboard Cite

IMPORTANCE Postoperative delirium is a frequent disorder for patients undergoing surgery and is associated with poor outcomes. Delirium may occur in the immediate period after anesthesia administration and surgery. Tropisetron, which is frequently administrated for postoperative nausea and vomiting, is also a partial agonist of α7 nicotinic acetylcholine receptors associated with neuroprotective effects. Tropisetron may be the potential pharmacological treatment to decrease delirium after noncardiac surgery. OBJECTIVE To perform a randomized clinical trial to determine the efficacy and safety of tropisetron for prevention of emergence delirium in patients undergoing noncardiac surgery. DESIGN, SETTING, AND PARTICIPANTS This single-center, 2-arm randomized, double-blind, placebo-controlled trial will include 1508 patients undergoing noncardiac surgery. The intervention group will receive 5 mg of intravenous tropisetron before anesthesia induction, and patients in the control group will receive a placebo. The primary end point is the incidence of emergence delirium within 1 hour after tracheal tube removal, measured by the Confusion Assessment Method for the Intensive Care Unit score. The main secondary outcome is the incidence of postoperative delirium measured at 3 days of follow-up. An intention-to-treat principle will be used for all analyses. DISCUSSION Delirium remains the most common neuropsychiatric complication for patients after surgery. This will be the first randomized clinical study to evaluate whether tropisetron is effective in preventing emergence delirium. Results from this study will provide evidence for alteration of daily practice. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04027751

show abstract

Tropisetron sensitizes α7 containing nicotinic receptors to low levels of acetylcholine in vitro and improves memory-related task performance in young and aged animals

Cited by 38 publications

References 50 publications

5-HT₃Receptor Antagonists in Neurologic and Neuropsychiatric Disorders: The Iceberg Still Lies beneath the Surface

5-HT₃Receptor Antagonists in Neurologic and Neuropsychiatric Disorders: The Iceberg Still Lies beneath the Surface

Tropisetron enhances recognition memory in rats chronically treated with risperidone or quetiapine

Effect of Tropisetron on Prevention of Emergence Delirium in Patients After Noncardiac Surgery

Contact Info

Product

Resources

About

Tropisetron sensitizes α7 containing nicotinic receptors to low levels of acetylcholine in vitro and improves memory-related task performance in young and aged animals

Cited by 38 publications

References 50 publications

5-HT3Receptor Antagonists in Neurologic and Neuropsychiatric Disorders: The Iceberg Still Lies beneath the Surface

5-HT3Receptor Antagonists in Neurologic and Neuropsychiatric Disorders: The Iceberg Still Lies beneath the Surface

Tropisetron enhances recognition memory in rats chronically treated with risperidone or quetiapine

Effect of Tropisetron on Prevention of Emergence Delirium in Patients After Noncardiac Surgery

Contact Info

Product

Resources

About

5-HT₃Receptor Antagonists in Neurologic and Neuropsychiatric Disorders: The Iceberg Still Lies beneath the Surface

5-HT₃Receptor Antagonists in Neurologic and Neuropsychiatric Disorders: The Iceberg Still Lies beneath the Surface