'heart-depressant' originates from English, specifically the compound of 'heart' and 'depressant', where 'heart' ultimately comes from Old English 'heorte' meaning 'heart', and 'depressant' derives from Latin 'deprimere' (via Old French/Middle English), where 'de-' meant 'down' and 'premere' (root of 'press') meant 'to press'.

'heart' changed from Old English 'heorte' to Middle English 'hert' and eventually became modern English 'heart'. 'Deprimere' in Latin led to Old French forms (e.g. 'depresser'), then to Middle English 'depress' and the derived noun/adjective 'depressant'; these elements were combined in modern English to form the compound 'heart-depressant' in usage related to medicine and physiology (19th–20th century onward).

Initially, the root idea meant 'to press down' (literally). Over time 'depressant' came to mean 'an agent that reduces activity or function', and when combined with 'heart' it evolved to mean specifically 'an agent that reduces heart activity' in medical contexts.