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P3‐450: Neurochemical profile of SUVN‐G1031, a novel histamine H3 receptor antagonist
Author(s) -
Muddageswararao,
Kandikere Vishwottam,
Bhyrapuneni Gopinadh,
Benade Vijay,
Hebballi Vijay,
Das Abinash,
Manjunath Lakshminarayana,
Ponnamaneni Ranjithkumar,
Manoharan Arunkumar,
Irappanavar Shantaveer,
Shinde Anil,
Nirogi Ramakrishna
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.1894
Subject(s) - neurochemical , histamine h3 receptor , histamine , pharmacology , antagonist , acetylcholine , prefrontal cortex , medicine , chemistry , receptor , neuroscience , psychology , cognition
farction in mice, and expected to be effective to other pathological conditions. Here, we assessed the possible effects of C21 on cognitive function to verify the possibility that AT2 receptor stimulation could contribute to enhancement of neural differentiation and protection after stroke, and neuronal survival and neurite outgrowth in response to ischemia-induced neuronal injury. Methods: Male 8-week-old C57BL6 and AT2 receptor-null (Agtr2 ) mice were treated with intraperitoneal injection of C21 (1, 3, 10 mg/kg/ day) once a day for 2 weeks. Then, mice were subjected to the Morris water maze test for 5 days to evaluate spatial memory. Cerebral blood flow was measured by 2 dimensional laser-Doppler. Field-excitatory postsynaptic potential (f-EPSP) was determined by electrophysiological techniques. Neurite elongation was assessed using hippocampal neurons prepared from GFP-transgenic mouse. Results: There were no significant differences in blood pressure and mRNA levels of AT1 and AT2 receptors between the mice treated with or without C21. Administration of C21 significantly enhanced spatial learning in C57BL6 mice, but this effect was not observed in Agtr2 mice. C21-mediated cognitive enhancement in C57BL6 mice was attenuated by co-administration of bradykinin B2 receptor antagonist, icatibant. Cerebral blood flow was significantly increased in C57BL6 mice with C21 treatment. Moreover, administration of C21 dose-dependently enhanced hippocampal EPSP in C57BL6 mice but not in Agtr2 mice. Furthermore, activation of the AT2 receptor by C21 alone or AT1 receptor blocker, irbesartan, under angiotensin II stimulation promoted neurite elongation of cultured hippocampal neurons. Conclusions: These results suggest that a direct AT2 receptor agonist, C21, is expected to enhance cognitive function with an increase in cerebral blood flow and an enhancement of EPSP with neurite elongation involving bradykinin 2 receptor activation.