Suppression of Cisplatin-Induced Vomiting by Cannabis sativa in Pigeons: Neurochemical Evidences

Abstract

Cannabis sativa (CS, family Cannabinaceae) has been reported for its anti-emetic activity against cancer chemotherapy-induced emesis in animal models and in clinics. The current study was designed to investigate CS for potential effectiveness to attenuate cisplatin-induced vomiting in healthy pigeons and to study the impact on neurotransmitters involved centrally and peripherally in the act of vomiting. High-performance liquid chromatography system coupled with electrochemical detector was used for the quantification of neurotransmitters 5-hydroxytryptamine (5HT), dopamine (DA) and their metabolites; Di-hydroxy Phenyl Acetic acid (Dopac), Homovanillic acid (HVA), and 5-hydroxy indole acetic acid (5HIAA) centrally in specific brain areas (area postrema and brain stem) while, peripherally in small intestine. Cisplatin (7 mg/kg i.v.) induce emesis without lethality across the 24 h observation period. CS hexane fraction (CS-HexFr; 10 mg/kg) attenuated cisplatin-induced emesis ∼ 65.85% (P < 0.05); the reference anti-emetic drug, metoclopramide (MCP; 30 mg/kg), produced ∼43.90% reduction (P < 0.05). At acute time point (3rd h), CS-HexFr decreased (P < 0.001) the concentration of 5HT and 5HIAA in the area postrema, brain stem and intestine, while at 18th h (delayed time point) CS-HexFr attenuated (P < 0.001) the upsurge of 5HT caused by cisplatin in the brain stem and intestine and dopamine in the area postrema. CS-HexFr treatment alone did not alter the basal neurotransmitters and their metabolites in the brain areas and intestine except 5HIAA and HVA, which were decreased significantly. In conclusion the anti-emetic effect of CS-HexFr is mediated by anti-serotonergic and anti-dopaminergic components in a blended manner at the two different time points, i.e., 3rd and 18th h in pigeons.

Bio-guided profiling and HPLC-DAD finger printing of Atriplex lasiantha Boiss

“…Natural resources represent an important reservoir of bioactive compounds for the development of novel drug entities [1–3]. Among natural sources, the plants have been used to cure majority of the ailments since ancient times.…”

Gingerol inhibits cisplatin-induced acute and delayed emesis in rats and minks by regulating the central and peripheral 5-HT, SP, and DA systems

“…* P < 0.05 vs. Group C, ‡ P < 0.05 vs. Group CG, † P < 0.05 vs. Group V, § P < 0.05 vs. Group M, || P < 0.05 vs. Group GL, ¶ P < 0.05 vs. Group GM. NEP neutral endopeptidase in dopamine, 5-HT and substance P receptors [42]. Endo et al [43] have suggested that 5-HT release from the enterochromaffin cells in ileum, accompanied by histopathological changes of the ileum mucosa, is involved in the onset of delayed emesis after administration of cisplatin.…”

Beyond the ‘purple drank’: Study of promethazine abuse according to the European Medicines Agency adverse drug reaction reports

“…Regarding the content of the ADR, according to the standardised MedDRA Query (SMQ) ( MedDRA, 2018 ), the following ADRs: dependence, drug abuse, drug abuser, drug dependence, drug withdrawal convulsions, drug withdrawal syndrome, drug withdrawal neonatal syndrome, intentional product misuse, intentional product use issue, substance abuse, substance abuser, substance use and withdrawal syndrome were selected. Those ADRs were defined in accordance with MedDRA in line with previous studies on the EV dataset ( Chiappini et al, 2020 ; MedDRA, 2018 ; Schifano and Chiappini, 2018a , 2018b ; Schifano et al, 2019a , 2019b ). Specifically, abuse was here defined as the intentional, non-therapeutic use by a patient or consumer of a product, OTC or prescription, for a perceived reward or desired non-therapeutic effect including, but not limited to, getting high (euphoria) ( MedDRA, 2018 ).…”

“…One of the limitations was given here by the descriptive nature of the study. Indeed, a comparator molecule, for a disproportionality analysis ( Chiappini and Schifano, 2016 ; Schifano and Chiappini, 2018b ) to be carried out, was not available due to data access limitations ( EMA, 2017 ; Postigo et al, 2018 ). Furthermore, current data did not appear to show an increasing trend of abuse or misuse across the years.…”