4'-[3-[(3R)-3-(Dimethylamino)-1-pyrrolidinyl]propoxy]-[1,1'-biphenyl]-4-carbonitrile dihydrochloride

Biological Activity

a-331440 is described here instead of a-331440 dihydrochloride. a-331440 is an antagonist of non-imidazole histamine h3 receptor with an ic50 value of 22.7 nm for human cortex histamine h3 [1].histamine, as a neurotransmitter, is important in homeostasis and physiology. in the cns, histamine released has the potential to interact with h1, h2, h3 and possibly h4 receptors. all the receptors are g-protein coupled receptors [2].in hek 293 cells stably transfected with rat or human histamine h3 receptors, a-331440 was tested for its ability to antagonize increasing calcium mobilization in response to (r)-α-methylhistamine and showed pkb ± s.e.m. values of 7.38 ± 0.10 and 7.37 ± 0.29 for rat histamine h3 and human histamine h3, respectively [1].in mice, treatment with a-331440 at a dose of 100 mg/kg resulted in piloerection and hypoactivity in the first 2 h, but diminished thereafter. in naive male cd-1 mice, administration with comparable doses of a-331440 i.p. also produced similar data. by day 28, mice treated with a-331440 at the intermediate dose weighed 35.7 ± 0.93 g with an average weight loss of 5.3 ± 0.99 g. the high dose of a-331440 (15 mg/kg, p.o., b.i.d.) produced a marked and sustained weight loss [1].

References

[1]. hancock aa, bennani yl, bush en, et al. antiobesity effects of a-331440, a novel non-imidazole histamine h3 receptor antagonist. european journal of pharmacology, 2004, 487(1): 183-197.
[2]. hancock aa, diehl ms, faghih r, et al. in vitro optimization of structure activity relationships of analogues of a-331440 combining radioligand receptor binding assays and micronucleus assays of potential antiobesity histamine h3 receptor antagonists. basic & clinical pharmacology & toxicology, 2004, 95(3): 144-152.