title: Synthesis and evaluation of analgesic, behavioral effects and chronic toxicity of the new 3,5-diaminopyrazole and its precursor the thiocyanoacetamide.
abstract: This study aimed to explore the analgesic, antioxidant, behavioral and toxicological effects of 3,5-diaminopyrazole and thiocyanoacetamide. Caffeine was used as reference drug whose effects are known after oral treatment with an efficient dose (10mg/kg/day) for 30days. The preliminary bioassays indicated that both compounds at this dose have strong antioxidant capacities and present highly analgesic effects. The behavioral study showed an activation of the rat memory by thiocyanoacetamide. This molecule caused a phobia state to open areas in the elevated plus maze and specifically agoraphobia in the open field with a lack in the development of the exploratory capacity. 3,5-Diaminopyrazole caused memory troubles in rats that forgot the pathway to the exit from the maze, and induced an anxiety state revealed by immobility in closed arms of the elevated plus maze. All these observations were compared to the treatment by the known analgesic, caffeine, which increased the state of vigilance of the rats and developed their exploratory capacity. The chronic treatment with the investigated compounds showed no sign of toxicity with the absence of effect on the body and organ weights, blood count, kidney and liver function and histology. 3,5-Diaminopyrazole and thiocyanoacetamide have potent antioxidant and analgesic activities that are higher than caffeine with a safety profile. The chronic treatment by thiocyanoacetamide activated the memory and caused an emotional state of agoraphobia, but 3,5-diaminopyrazole caused a memory impairment and an emotional state of anxiety. Thus, the present study warrants further investigations involving these novel molecules for a possible development of new strong analgesic and antioxidant drugs which have an effect on the memory capacity.
authors.affiliation: Experimental Medicine Unit, School of Medicine of Tunis, University of Tunis El Manar, Tunisie. Electronic address: ridhabenali9@gmail.com.
authors.forename: Ridha
authors.initials: R
authors.lastname: Ben Ali
authors.affiliation: Experimental Medicine Unit, School of Medicine of Tunis, University of Tunis El Manar, Tunisie.
authors.forename: Amal
authors.initials: A
authors.lastname: Ben Othman
authors.affiliation: Laboratory of Organic Synthesis and Heterocyclic Chemistry Department, School of Sciences of Tunis, University of Tunis El Manar, Tunisie.
authors.forename: Khouloud
authors.initials: K
authors.lastname: Bokri
authors.affiliation: Laboratory of Physiology, School of Medicine of Tunis, University of Tunis El Manar, Tunisie.
authors.forename: Samira
authors.initials: S
authors.lastname: Maghraoui
authors.affiliation: National Laboratory of Drug Control Tunis, Tunisie.
authors.forename: Adel
authors.initials: A
authors.lastname: Hajri
authors.affiliation: Laboratory of Organic Synthesis and Heterocyclic Chemistry Department, School of Sciences of Tunis, University of Tunis El Manar, Tunisie.
authors.forename: Azaiez
authors.initials: A
authors.lastname: Ben Akacha
authors.affiliation: Experimental Medicine Unit, School of Medicine of Tunis, University of Tunis El Manar, Tunisie.
authors.forename: Chadli
authors.initials: C
authors.lastname: Dziri
authors.affiliation: Experimental Medicine Unit, School of Medicine of Tunis, University of Tunis El Manar, Tunisie; Histology, Embryology and Cell Biology Laboratory, School of Medicine of Tunis, University of Tunis El Manar, Tunisie.
authors.forename: Michèle Véronique
authors.initials: MV
authors.lastname: El May
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D009570:Nitriles / Q000138:chemical synthesis / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D036401:Toxicity Tests, Chronic / Q000379:methods*
chemical_list: D000700:Analgesics; D009570:Nitriles; D011720:Pyrazoles; C031594:2-cyanoacetamide
keywords: 3,5-diaminopyrazole and thiocyanoacetamide; Analgesic; Antioxidant; Behavioral effect; Safety profile