If you are on a 64bit OS then you are 'silently' remote debugging. Devenv runs in WoW64 (meaning it's a 32bit process) ... when you hit F5 is launchs msvsmon.exe as a 64 bit process and sets up a communication channel between devenv and msvsmon "silent remote debugging" to allow debugging your 64 bit process.
Check task manager when you are successfully debugging and you should see msvsmon.exe running.
If the above assumption (64bit OS) is correct, the error you are seeing is based on Visual studio getting into a bad state. If it gives this error while an msvsmon.exe instance is running ... kill that instance. If there is no msvsmon.exe running, then restarting devenv is probably your only option.
Another possible workaround is to set your project to 'platform x86' so that you are directly debugging. The x86 compiled managed assemblies or native binaries will run in Wow64, and prevent any need for the silent remote debugging. (Obviously this doesn't help if it is a 64-bit only problem ... but in practice that is rare.)
I hope this helped or can assist you in searching out a better answer.
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