[TRH analogs at Gedeon Richter Ltd.: highlights of experimental and clinical efficacy of posatirelin].
The chemical research for dissociation of the central nervous system effects of thyrotropin-releasing hormone (TRH) from its hormonal activity resulted in the selection of RGH-2202 (posatirelin) for further development. Posatirelin showed stronger vigilance enhancing effect than TRH in a variety of commonly used neuro-psychopharmacological model in mice, rats and cats. This drug had positive effects in animal models of disturbed consciousness, and counteracted the decline of learning and memory capacity shown by aged or memory impaired rats. Posatirelin had a trophic effect on neurons both 'in vitro' and 'in vivo' as well. Activation of various neurotransmission systems has been demonstrated, but the "modulatory" action of this neuropeptide-like compound is too complex to be explained by a single mechanism. Posatirelin practically had no hormonal activity or other significant side effects either in animal studies or in clinical trials. The arousal level increasing and the neuronotrophic effects appeared in part in trials of human brain injuries and cerebral infarction. Patients suffering in dementia syndromes of either vascular or degenerative origin and treated chronically with posatirelin showed significant improvement in intellectual performance, in orientation, motivation and memory function in all well controlled trials.
Sarkadi
Adám
A
Richter Gedeon Rt., Budapest.
Kárpáti
Egon
E
D000818:Animals; D001143:Arousal / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy*; D006801:Humans; D007858:Learning / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects*; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use*
D013973:Thyrotropin-Releasing Hormone; C055448:posatirelin