A possible role for tyramines in brain function and some mental disorders.

The administration of antlpsychotlc drugs to the mouse caused a reduction in stnatal p-tyramme but did not change or increase m-tyramlne, these effects were observed for drugs such as chlorpromazlne, thioproperazlne, fluphenazine, halopendol, splperone, mohndone at low doses, ~-flupenthlxol and (+)-butaclamol (Juono, 1977a, 1979a, 1980a, Boulton & Juorlo, 1979) In contrast, the administration of structurally related but clinically inactive compounds (promethazme, fl-flupenthixol, and (-)-butaclamol) did not cause any significant changes in stnatal por m-tyramlne levels (Juorio, 1977a) Similar effects were observed in the rat striatum following administration of fluphenazme, haloperidol or mohndone at low doses (Juorlo & Danielson, 1978, Juorio, 19801 The administration of some antlpsychotics to mice pretreated with tranylcypromine or clorgyhne produced a significant reduction in stnatal p-tyramine when compared with the concentrations obtained in mice given a monoamlne oxldase inhibitor alone (Juorio, 1979a), such results suggest that antlpsychotlcs reduced striatal p-tyramine formation The moderate increases produced by monoamlne oxldase inhibition on stnatal m-tyramme were not significantly changed after the administration of the antlpsychotlcs drug (Juorlo, 1979a) The administration of d-amphetamine to rats causes a significant reduction in p-tyramine concentrations in the stnatum and the olfactory lobes (Danielson et al, 1976) while m-tyramine was increased in both regions Because neuroleptlc drugs counteract the behavloural effects of d-amphetamine (Randrup et al, 1963, Espehn & Done, 1968), the effects on strlatal tyramlne levels of d-amphetamine injected into mice pre-treated with either chlorpromazine or haloperldol (Juono, 1977b) were investigated Initially surprising was the observation that the reduction in p-tyramine was potentiated while the m-tyramlne concentration was increased (Juorio, 1977b) An explanation for this phenomenon could be that p-tyramine, m-tyramlne and dopamine are reciprocally related, and that both d-amphetamine and antlpsychotIcs increase dopamlne turnover (Juono, 1980b) The mechanisms by which ttiese increases are produced are not the same, d-amphetamine increases the release of dopamlne and blocks its reuptake, thus increasing the formation of homovanilhc acid (Jorl & Bernardi, 1969, 1972, Costa et al, 1972) Neuroleptic