RESEARCH
Up and Down with DPN Nucleotide m a y be a reason for anxiety and de pressed states; action linked to tranquilizers
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ACS NATIONAL MEETING Biological Chemistry
Behind our ups and downs m a y lurk d i e coenzyme D P N ( d i p h o s p h o p y r i d i n e n u c l e o t i d e ) . It may well be t h a t the a m o u n t of this coenzyme in our b o d y tissues governs the biochemical mecha nisms w h i c h lead to anxious a n d de pressed states in humans—the higher t h e D P N level, the more t r a n q u i l the individual. This is t h e crux of a hypothesis pro posed by Richard Salvador a n d Robert Main Burton, W a s h i n g t o n University of St. Louis, before a s y m p o s i u m on enzymes a n d coenzymes p r e s e n t e d by t h e Division of Biological Chemistry. Salvador explains t h a t the c l u e to this idea c a m e u p when he a n d his co workers found that nicotinamide (a B vitamin) acts synergistically w i t h tran quilizers such as reserpine a n d chlorpromazine. This increased activity is probably due to more t h a n normal amounts of D P N b e i n g f o r m e d in the b o d y : h e n c e . D P N may b e linked to tranquilizer mechanisms in t h e body. Nicotinamide takes part in oxidation
and reduction reactions in the body. In coenzyme forms such as D P N , it re acts enzyrnatically with many s u b stances. For example, it reduces u n saturated fatty acids or oxidizes ster oids, thus plays a vital role in t h e metabolism of sugars, fats, and steroids and in the transport of electrons from substrates to oxygen with the conserva tion of energy as adenosine triphos phate. W h e n nicotinamide is injected into mice, the D P N level in tissues goes u p , reaching a maximum in 10 to 12 hours and returning to basal levels within 24 hours. W h e n a tranquilizer is admin istered along with the vitamin, the D P N levels are higher for more than 4 8 hours. F u r t h e r studies, Salvador continues, show that the spontaneous activity of mice is reduced greatly by administer ing both the tranquilizer and nicotin amide rather than giving either alone. Researcher Salvador adds also that bar biturate-induced anesthesia is pro longed by the tranquilizer-nicotinamide combination. • Biochemical M e c h a n i s m . To pin point the mechanism leading to the high tissue levels of D P N , Salvador and
coworkers gave r a d i o a c t i v e nicotin amide to rats who h a d been pretreated with cUhlorrpromazine or reserpine. After 24 hours, the livers of the tranquilized animals h a d more radio activity than tlmse of noniranquilized rats because of m o r e D P N being made. (Some of t h e radioactive com pounds have "been isolated a n d are still being studied, Salvador explains.) From what i s known thus far, h e con tinues, the bioc-Leu* ical mechanism goes like this: In the body, nicotinamide forms metabolites such as pyridone, trigenellin, and .Vinedhyl nicotinamide. T h e vitamin is also a n intermediate to make D P X . But when r-esirpine or chlorpromazine is added, the synthesis of nicotin amide metabol ites is blocked, and more nicotinamide joins the D P N intermedi ates with thee*nrh-f*sul-t being a large in crease in theparodixction of D P N . Also, tranquilizer activity is lengthened; this suggests that DPN is implicated in tranquilizer in«dii«.nisrns. These studies, t h e n , Salvador con cludes, may help to u n d e r s t a n d how tranquilizers work in the body as well as explain the? enzymatic pathways to the synthesis of D P N T - a topic not too well known to»
