Anticonvulsant effect of DN-1417, a derivative of thyrotropin-releasing hormone, and liposome-entrapped DN-1417, on amygdaloid-kindled rats.

The effects of gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-propionamide citrate (DN-1417), a derivative of thyrotropin-releasing hormone, and liposome-entrapped DN-1417 (DN-L) were examined in amygdaloid-kindled rats. The animals were tested 2 h after intraperitoneal (i.p.) drug administration and then again every 24 h without further drug treatment. DN-1417 did not suppress the kindled seizure at 2 h but did beginning 1-6 days after injection. DN-L suppressed the kindled seizure at 2 h and had a more prolonged anticonvulsant effect than DN-1417. After liposomes were given i.p. once daily for 2 weeks, there was no morphologic evidence that liposomes damaged brain neurons. These results, together with previously published data, suggest that as drug delivery vehicles, liposomes can enhance the effectiveness of drugs in the CNS without producing overt brain damage.