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The origin of Panicale is ancient, the first settlements date from the second millennium BC, while documented the presence of the Etruscans in the seventh century BC. In Roman times was when a military camp where some fled Romans fled from Perugia because of war between Lucio Antonio (brother of Marco Antonio) and Octavian (Bellum perusinum).
In the history of medieval castle Panicale is closely linked to that of Perugia, both economically and militarily. Indeed Panicale is both an important centre for the supply of food (bread and meat), is an outpost west of Perugia. It is the first municipality free of Italy and in 1037 achieved independence from Uguccione II Duke of Bourbon. In the thirteenth century submits to the Lordship of Perugia, although he had a discreet autonomy. Done very important is the first compilation of a Statute (1316), written in Latin by the notary Pierre Vannuccio Vannucci, which will be developed and modified in 1356 and in 1386. In 1484 the Statute will be translated into vernacular to facilitate understanding to the citizens. From 1416 to 1424 the captain venture arm by Montone is lord of Perugia and consequently also governs Panicale, which will start as a long series of Signorie that assoggetteranno for many years. During the Renaissance Panicale lives a period of economic development, territorial expansion and general welfare, which allows the execution of various works of art by famous artists such as Il Perugino.
In 1540 Perugia is conquered by the papal state that will maintain control over the area (then Panicale included) up to Italy, except for the Napoleonic years. It introduced new laws, rules and regulations which will replace the old Statute of 1316.
The seventeenth century is Panicale a century of slow decline. On 11 and May 12, 1798 the Napoleonic army enters into Panicale and decrees the suspension of papal power.
In 1860 was annexed to the Kingdom of Italy.
 
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