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Objective: The involvement of imidazoline receptors in the effect of agmatine was studied in locomotor recovery following experimental SCI (ESCI) in mice. Methods: ESCI was induced in mice using compression method. Locomotor function score (0-10) was measured on day 14 following ESCI. Results: Agmatine (2.5, 5, and 10 mg/kg) treatment through intraperitoneal route for 14 days following ESCI, dose-dependently improved the motor function score. Clonidine (0.1 mg/kg; imidazoline I1 receptor agonist) or moxonidine (0.5 mg/kg; I2 receptor agonist) treatment 15 min before agmatine (2.5 mg/kg) daily for 14 days, following ESCI, significantly potentiated the effect of per se agmatine. On the other hand, 15 min before treatment of efaroxan (1 mg/kg; imidazoline I1 receptor antagonist) or idazoxan (3 mg/kg; imidazoline I2 receptor antagonist) significantly blocked the motor function score of agmatine (10 mg/kg). Conclusion: These data suggest that imidazoline receptors may modulate the locomotor recovery following ESCI in agmatine treated mice, perhaps through I1/I2 receptors. [ABSTRACT FROM AUTHOR]

Nicotine abstinence following chronic exposure is associated with impairments in memory and variety of cognitive functions. Daily nicotine (2 mg/kg, sc, four times daily) administration for 14 days and its abrupt withdrawal significantly impaired avoidance learning in inhibitory avoidance task as indicated by a significant decrease in the step through latency. Animals injected with agmatine (10–40 μg/rat, icv) from day 7 to 14 before the first daily dose of nicotine (2 mg/kg, sc) showed increased step through latencies during retrieval test. Similarly Intracerebroventricular injection of l -arginine (25–100 μg/rat), a biosynthetic precursor of agmatine and arcaine (50 μg −100 μg/rat), an agmatinase inhibitor, also increased the step through latency during retrieval test in nicotine withdrawn animals. In separate experiments, α 2 -adrenoceptor agonist, clonidine (0.5–1 μg/rat, icv) not only demonstrated significant increase in the step through latency as in nicotine withdrawn rats but also potentiated the pharmacological effect of agmatine. In contrast, pre-treatment of α 2 -adrenoceptor antagonist, yohimbine (0.5 μg/rat, icv) antagonized the memory enhancing effect of agmatine (20 μg/rat, icv) in nicotine withdrawn rats. In addition, brain agmatine analysis carried out at 72 h time point of nicotine withdrawal showed marked decrease in basal brain agmatine content as compared to control. Overall, the data indicate that agmatine attenuates nicotine withdrawal induced memory impairment through modulation of α 2 adrenergic receptors. Thus, agmatine might have therapeutic implications in the treatment of cognitive deficits following nicotine withdrawal. [ABSTRACT FROM AUTHOR]

Introduction: Alginates can be tailored chemically to improve solubility, physicochemical, and biological properties and its complexation with metal ion is useful for controlling the drug release. Materials And Methods: Synthesized N,O-dimethyl, N-methyl, or N-Benzyl hydroxylamine derivatives of sodium alginate were subsequently complexed with zinc to form beads. Hydroxamation of sodium alginate was confirmed by Fourier transform infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results: The synthesized polymeric material exhibited reduced aqueous, HCl and NaOH solubility. The hydroxamated derivatives demonstrated pulsed release where change in pH of the dissolution medium stimulated the atenolol release. Conclusion: Atenolol loaded Zn cross-linked polymeric beads demonstrated the sustained the plasma drug levels with increased half-life. Although the synthesized derivatives greatly altered the aqueous solubility of sodium alginate, no significant differences in in vitro and in vivo atenolol release behavior amongst the N,O-dimethyl, N-methyl, or N-Benzyl hydroxylamine derivatives of sodium alginate were observed. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is an age related progressive neurodegenerative disorder characterized by decline in cognitive functions, such as memory loss and behavioural abnormalities. The present study sought to assess alterations in agmatine metabolism in the beta-amyloid (Aβ 1-42 ) Alzheimer's disease mouse model. Aβ 1-42 injected mice showed impairment of cognitive functioning as evidenced by increased working and reference memory errors in radial arm maze (RAM). This cognitive impairment was associated with a reduction in the agmatine levels and elevation in its degrading enzyme, agmatinase, whereas reduced immunocontent was observed in its synthesizing enzyme arginine decarboxylase expression within hippocampus and prefrontal cortex. Chronic agmatine treatment and its endogenous modulation by l-arginine, or arcaine or aminoguanidine prevented the learning and memory impairment induced by single intracranial Aβ 1-42 peptide injection. In conclusion, the present study suggests the importance of the endogenous agmatinergic system in β-amyloid induced memory impairment in mice., (Copyright © 2020 Elsevier B.V. All rights reserved.)