In 1744 Bishop Francisco Javier de Luna Victoria y Castro established the College of San Ignacio de Loyola and on June 3, 1749 founded La Real y Pontificia Universidad de San Javier. By this time, however, Panama’s importance and influence had become insignificant as Spain’s power dwindled in Europe and advances in navigation technique increasingly permitted to round Cape Horn in order to reach the Pacific. While the Panama route was short it was also labor intensive and expensive because of the loading and unloading and laden-down trek required to get from the one coast to the other.
The Panama route was also vulnerable to attack from pirates (mostly Dutch and English) and from 'new world' Africans called cimarrons who had freed themselves from enslavement and lived in communes or palenques around the Camino Real in Panama's Interior, and on some of the islands off Panama's Pacific coast. During the last half of the Eighteenth century and the first half of the Nineteenth century, migrations to the countryside decreased Panama City’s population and the isthmus' economy shifted from the tertiary to the primary sector.
In 1717, the viceroyalty of New Granada (northern South America) was created in response to other Europeans trying to take Spanish territory in the Caribbean region. The Isthmus of Panama was placed under its jurisdiction. But the remoteness of Santa Fe de Bogota proved a greater obstacle than the Spanish crown anticipated as the authority of New Granada was contested by the seniority, closer proximity, previous ties to the viceroyalty of Lima and even Panama's own initiative. This uneasy relationship between Panama and Bogota would persist for century or two.
Modern Panamanian history has been shaped by its transisthmian canal, which had been a dream since the beginning of Spanish colonization. From 1880 to 1890, a French company under Ferdinand de Lesseps attempted unsuccessfully to construct a sea-level canal on the site of the present Panama Canal.
On the other hand, the Panamanian movement for independence can be indirectly attributed to the abolishment of the encomienda system in Azuero, set forth by the Spanish Crown, in 1558 because of repeated protests by locals against the mistreatment of the native population. In its stead, a system of medium and smaller-sized landownership was promoted, thus taking away the power from the large landowners and into the hands of medium and small sized proprietors.
The end of the encomienda system in Azuero, however, sparked the conquest of Veraguas in that same year. Under the leadership of Francisco Vázquez, the region of Veraguas passed into Castillan rule in 1558. In the newly conquered region, the old system of encomienda was imposed.