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Tandamine is a selective norepinephrine reuptake inhibitor with a tricyclic structure. It was developed in the 1970s as an antidepressant but was never commercialized. Tandamine is analogous to pirandamine, which, instead, acts as a selective serotonin reuptake inhibitor (SSRI).
When the indole 3-position is already substituted, electrophilic reagents attack the 2-position instead often through a 3,3-spiro intermediate. For example, when 2-(3-indolyl)ethylmercaptan (1) reacts with methyl acetoacetate, the thia-β-carboline analogue (#) results. It seems plausible that the reaction involves initial hemithioketal formation (2), followed by release by the indole nitrogen and hydroxide displacement to give 3 has interupted aromaticity, and a Wagner-Meerwein rearrangement would lead to carbonium ion 4, which would eject a proton to restore indole resonance (#). In anycase (#) is the product. Saponification to the free acid (#) is followed by dimethylamide formation (6), mediated by carboxyl activation via mixed anhydride reaction with ethyl chlorocarbonate. LAH reduction to the 3° amine () is followed by base-mediated N-alkylation with ethylbromide to produce tandamine (7), an thymoleptic that inhibits the uptake of NA into storage granules.
- Lippmann W, Pugsley TA (May 1976). "The effects of tandamine, a new potential antidepressant agent, on biogenic amine uptake mechanisms and related activities". Biochemical Pharmacology 25 (10): 1179–86. doi:10.1016/0006-2952(76)90366-X. PMID 1084746.
- Ehsanullah RS, Ghose K, Kirby MJ, Turner P, Witts D (March 1977). "Clinical pharmacological studies of tandamine, a potential antidepressive drug". Psychopharmacology 52 (1): 73–7. doi:10.1007/BF00426603. PMID 403562.
- Pugsley TA, Lippmann W (September 1979). "Effect of acute and chronic treatment of tandamine, a new heterocyclic antidepressant, on biogenic amine metabolism and related activities". Naunyn-Schmiedeberg's Archives of Pharmacology 308 (3): 239–47. doi:10.1007/BF00501388. PMID 503251.
- Pugsley T, Lippmann W (May 1976). "Effects of tandamine and pirandamine, new potential antidepressants, on the brain uptake of norepinephrine and 5-hydroxytryptamine and related activities". Psychopharmacology 47 (1): 33–41. doi:10.1007/BF00428698. PMID 1085452.
- Lippmann W, Seethaler K (April 1977). "Effects of tandamine and pirandamine, selective blockers of biogenic amine uptake mechanisms, on gastric acid secretion and ulcer formation in the rat". Life Sciences 20 (8): 1393–400. doi:10.1016/0024-3205(77)90367-8. PMID 853871.
- D. A. Demerson, DE 2301525 (1975)
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