![]() ![]() Subsequent studies indicated that TPM possesses a long duration of action in mice and rats, with a wide separation between the effective anticonvulsant doses and doses that cause motor impairment. In late 1979, TPM was tested for possible anticonvulsant activity in the traditional maximal electroshock seizure (MES) test in mice and found to be highly active. Compounds with this activity would inhibit gluconeogenesis and thereby have potential as antidiabetic agents. Topiramate (TPM TOPAMAX ®) was first synthesized in 1979 by researchers in the pharmaceutical division of Johnson & Johnson as part of an effort to discover structural analogues of fructose-1,6-diphosphate that could inhibit the enzyme fructose 1,6-bisphosphatase. ![]() adenosine 5′-monophosphate-activated protein kinase. ![]()
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![]() With Edward Weevil and Bakkin hunting for Whitebeard's inheritance, Marco anticipated that they would attack this place, and so elected to stay behind and protect it instead of joining the Ninja-Pirate-Mink-Samurai Alliance against Kaidou. Marco revealed that Sphinx was Whitebeard's homeland and his last keepsake. Nekomamushi and the Guardians arrived on Sphinx, where Marco resided and worked as a doctor.
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