This study aimed at evaluation of the reactivity of melatonin (1) towards various chemical reagents to produce new melatonin analogues containing heterocyclic moieties which would provide basic pharmacological activities. The pyrrolo[1,2-a]indole derivatives 3, 5, 12, 14 and pyrido[1,2-a]indole derivatives 9a, b were synthesized via straightforward and efficient methods and their structures were established based on the analytical and spectral data. Also, this work was extended to study the potential role of the novel synthesized melatonin analogues 3, 5, 9a and 12 as anti-inflammatory and anti-nociceptive agents in comparison with melatonin. After s.c. administration all compounds induced significant anti-inflammatory activity, inhibiting the paw oedema response compared with the control group at all time points in the test. Compound 5 has the strongest anti-inflammatory activity which exceeds that of the parent reference, melatonin, followed by compounds 9a and 12, at the first 2h of administration. Effect of melatonin analogues on thermal pain, acetic acid-induced writhing and gastric lesions caused by indomethacin was also investigated. Compounds 5 and 12 were more potent as anti-nociceptive drugs; they are more potent in this respect than melatonin.