Responding to the need for push-pull locomotives, units E.646 187 to 210 were manufactured with control circuits and connectors to be remotely commanded.

The E.645 had a different gear ratio — 21/68 instead of 25/64 — which reduced the maximum speed to 120 km/h (75 mph), while increasing tractive effort.

The rheostat was gradually shunted as speed builds up and is also reintroduced when a transition to another motor configuration is made; like almost every Italian electric locomotive since the E.626, rheostatic shunting was achieved through a controller (a lever mounted on a curved notched support, commonly called respectively maniglione and roncola in Italian) with several notches, each representing a portion of the rheostat, plus four (one for each combination) special intermediate "end combination" notches.

The driver gradually shunted the rheostat by rotating the lever counterclockwise, paying attention to not exceed the maximum allowed current (in that case, the "maximum current relay", and consequently the "Main Breaker" - IR, Interruttore Rapido - opens), until he reached the end combination notches, meaning that the rheostat is fully shunted for that combination; at this point, he could pass to the following combination or insert the field weakening shunts to further increase the motor current.

Air pressure was provided by two 1,000 L (260 US gal) compressors that filled the main tanks used by the braking system and other components (horn, whistle, contactors etc.).

For testing purposes, units E.645.016 and 017 were built with an even shorter gear ratio (20/69) that allowed a maximum speed of 110 km/h (68 mph).

The train hauled by the two locomotives derailed due to damage to the line caused by a landslide, and ended poised over a slope.

In Florence Firenze Castello station, on March 23, 1998, unit E.646.009 was hit by EMU ETR 480-34, that was running between Rome and Bergamo, and that passed a signal at 'danger' without stopping (SPAD); the accident caused one dead and 39 wounded.