Lometraline Explained

Lometraline (INN; developmental code name CP-14,368) is a drug and an aminotetralin derivative.^[1] A structural modification of tricyclic neuroleptics, lometraline was originally patented by Pfizer as an antipsychotic, tranquilizer, and antiparkinsonian agent.^{[2] [3]} However, it was instead later studied as a potential antidepressant and/or anxiolytic agent, though clinical studies revealed no psychoactivity at the doses used and further investigation was suspended.^{[4] [5]} Further experimental modifications of the chemical structure of lometraline resulted in the discovery of tametraline, a potent inhibitor of the reuptake of dopamine and norepinephrine, which in turn led to the discovery of the now widely popular antidepressant sertraline, a selective serotonin reuptake inhibitor (SSRI).^[6]

The precursor ketone can undergo a Mannich reaction with pyrrolidine to yield CID:12348935. This specific agent had analgesic activity in the same range as morphine and was not antagonized by naloxone.^{[7] [8]}

Notes and References

1. Park S, Gershon S, Angrist B, Floyd A . Evaluation of an aminotetraline, CP 14.368, as an antidepressant . Current Therapeutic Research, Clinical and Experimental . 14 . 2 . 65–70 . February 1972 . 4401233 .
2. Book: Drake E . Saunders pharmaceutical word book, 1994 . 27 April 2012 . 27 January 1994 . W.B. Saunders Co. . 978-0-7216-5254-2.
3. Book: United States. Patent Office . Lometraline: tranquillizer, anti-parkinson agent . Official gazette of the United States Patent Office: Patents . 27 April 2012 . 1972 . The Office.
4. Book: McMahon FG . Psychopharmacological agents . 27 April 2012 . 1974 . Futura Pub. Co. . 978-0-87993-052-3 .
5. Book: Bayerische Julius-Maximilians-Universität Würzburg. Arbeitskreis für Schlafforschung . The Nature of sleep. Die Natur des Schlafes. La nature du sommeil: International symposium, Würzburg, 23-26.9.1971 . 27 April 2012 . 1973 . G. Fischer . 978-3-437-10295-0.
6. Web site: Discovery of sertraline (Zoloft®) . Koe BK, Harbert CA, Sarges R, Weissman A, Welch WM . 2006 . 2012-04-27 . https://web.archive.org/web/20141230213550/http://oasys2.confex.com/acs/231nm/techprogram/P936639.htm . 2014-12-30 . dead .
7. Welch WM, Harbert CA, Sarges R, Stratten WP, Weissman A . Analgesic and tranquilizing activity of 5,8-disubstituted 1-tetralone Mannich bases . Journal of Medicinal Chemistry . 20 . 5 . 699–705 . May 1977 . 853506 . 10.1021/jm00215a016 .
8. Welch WM, Plattner JJ, Stratten WP, Harbert CA . Analgesic and tranquilizing activity of 5,8-disubstituted 2-aminomethyl-3,4-dihydronaphthalenes . Journal of Medicinal Chemistry . 21 . 3 . 257–63 . March 1978 . 628000 . 10.1021/jm00201a004 .