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New headache drugs differ in mechanism from aspirin in several ways. Aspirin, also known as acetylsalicylic acid, is a non-steroidal anti-inflammatory drug (NSAID) that works by inhibiting the production of prostaglandins, which are hormone-like substances that cause inflammation and pain [3].

On the other hand, newer headache drugs, such as monoclonal antibodies and CGRP (calcitonin gene-related peptide) antagonists, work through different mechanisms. These drugs target the nervous system and block the activity of CGRP, a molecule that is involved in the transmission of pain signals in the brain [1][2].

Monoclonal antibodies, such as erenumab, galcanezumab, and fremanezumab, are administered via injection and can prevent migraines from occurring [1]. CGRP antagonists, such as ubrogepant and rimegepant, are taken orally and can be used to treat acute migraines [1].

In contrast to aspirin, which can have side effects such as stomach ulcers and bleeding, the newer headache drugs have different side effect profiles. The most common side effects of monoclonal antibodies include injection site reactions, while the most common side effects of CGRP antagonists include nausea and constipation [1].

In summary, new headache drugs differ in mechanism from aspirin by targeting the nervous system and blocking the activity of CGRP, as opposed to aspirin's mechanism of inhibiting the production of prostaglandins. This results in different side effect profiles and potential uses for preventing or treating migraines.

Sources:

[1] <https://www.yalemedicine.org/news/acetaminophen-nsaids-over-the-counter-pain-relievers>

[2] <https://www.ncbi.nlm.nih.gov/books/NBK547742/>

[3] <https://www.drugpatentwatch.com/p/tradename/ASPIRIN>