2-MDP explained

2-MDP (U-23807A) is a dissociative anaesthetic drug which has been found to be an NMDA antagonist and produces similar effects to PCP in animals. The levo or (−)-isomer is the active form of the drug.^{[1] [2]} It also has stimulant effects, having only around one third the potency of amphetamine by weight, but with a long duration of action, lasting more than 24 hours from a single oral dose.^[3]

Effects

The therapeutic action is said to exhibit appetite suppressant- and antidepressant-like activity.^[4]

Synthesis

In a variation of the nitrile-aldol reaction, combination of benzophenone (1) and propionitrile (2), in the presence of sodamide base and ethyl ether solvent, leads to 3-hydroxy-2-methyl-3,3-diphenylpropanenitrile (3).^[5] The reduction of the intermediate nitrile group with lithium aluminium hydride completes the synthesis of 2-MDP (4).

Notes and References

1. Tang AH, Cangelosi AA, Code RA, Franklin SR . Phencyclidine-like behavioral effects of 2-methyl-3,3-diphenyl-3-propanolamine (2-MDP) . Pharmacology, Biochemistry, and Behavior . 20 . 2 . 209–213 . February 1984 . 6718449 . 10.1016/0091-3057(84)90244-2 . 38908019 .
2. Blake JC, Davies SN, Church J, Martin D, Lodge D . 2-Methyl-3,3-diphenyl-3-propanolamine (2-MDP) selectively antagonises N-methyl-aspartate (NMA) . Pharmacology, Biochemistry, and Behavior . 24 . 1 . 23–25 . January 1986 . 3511477 . 10.1016/0091-3057(86)90038-9 . 29762524 .
3. Biel JH . Antidepressants, Stimulants, Hallucinogens. . Cain CK . Annual Reports in Medicinal Chemistry . January 1967 . 2 . 11–23, 18 . Academic Press . 10.1016/S0065-7743(08)61499-2 .
4. Shipley GS, Bishop MP, Gallant DM . A controlled evaluation of U-23,807A in the neurotic depressive syndrome . Current Therapeutic Research, Clinical and Experimental . 9 . 10 . 514–516 . October 1967 . 4964946 .
5. Moffett RB, Pickering TL . Central nervous system agents. 2. Synthesis of diphenyl primary and secondary aminopropanols . Journal of Medicinal Chemistry . 14 . 11 . 1100–1106 . November 1971 . 5115211 . 10.1021/jm00293a019 .