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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Anticonvulsant activity of a nonpeptide galanin receptor agonist.

Galanin is a neuropeptide with a wide variety of biological functions, including that of a strong endogenous anticonvulsant. No nonpeptide ligands, capable of activating galanin receptors, are available today. Based on known pharmacophores of galanin, a combinatorial library was designed, synthesized, and screened at the rat hippocampal galanin receptor. A low molecular weight galanin receptor agonist, 7-((9-fluorenylmethoxycarbonyl)cyclohexylalanyllysyl)amino-4-methylcoumarin (galnon) was found to displace (125)I-galanin with micromolar affinity at Bowes cellular and rat hippocampal membranes. Autoradiographic binding assay on rat spinal cord sections confirmed the ability of galnon to displace (125)I-galanin from its binding sites. Galnon inhibited adenylate cyclase activity, suggesting an agonist action at galanin receptors. When injected i.p. galnon reduced the severity and increased the latency of pentylenetetrazole-induced seizures in mice and reversed the proconvulsant effects of the galanin receptor antagonist M35, injected into a lateral ventricle. Intrahippocampal injection of galnon also shortened the duration of self-sustaining status epilepticus in rats, confirming its agonist properties in vivo. Pretreatment of rats with antisense peptide nucleic acid targeted to galanin receptor type 1 mRNA abolished the effect of galnon, suggesting mediation of its anticonvulsant properties through this receptor subtype. These findings introduce a systemically active nonpeptide galanin agonist anticonvulsant.[1]


  1. Anticonvulsant activity of a nonpeptide galanin receptor agonist. Saar, K., Mazarati, A.M., Mahlapuu, R., Hallnemo, G., Soomets, U., Kilk, K., Hellberg, S., Pooga, M., Tolf, B.R., Shi, T.S., Hökfelt, T., Wasterlain, C., Bartfai, T., Langel, U. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
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