clozapine and tipepidine

We previously reported that centrally acting non-narcotic antitussives, including tipepidine, inhibit G-protein-coupled inwardly rectifying potassium (GIRK) channel-activated currents of neurons. In addition, when administered at a cough suppressant dose, the drugs ameliorated the symptoms of various models of intractable brain disease in rodents. In the current study, we investigated whether tipepidine causes recovery from schizophrenia-like cognitive dysfunction, which was induced by MK-801 (0.2 mg/kg, i.p.) in mice. We also examined the effect of tipepidine and clozapine co-administration on the dysfunction. Moreover, we studied whether clozapine inhibits GIRK channel activated currents in single brain neurons using the patch-clamp technique. Tipepidine elicited recovery from MK-801-induced cognitive impairment in the novel objective recognition test and Y-maze test. Further, co-administration of tipepidine and clozapine, at subthreshold doses of each drug, improved MK-801-induced cognitive impairment in the novel objective recognition test. Clozapine (3 × 10

Topics: Animals; Antidepressive Agents; Antitussive Agents; Clozapine; Cognitive Dysfunction; Disease Models, Animal; Dizocilpine Maleate; Dopaminergic Neurons; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Male; Mice; Patch-Clamp Techniques; Piperidines; Rats; Rats, Wistar; Schizophrenia; Ventral Tegmental Area