Effect of antidepressant drugs on the depletion of intraneuronal brain 5-hydroxytryptamine stores caused by 4-methyl-α-ethyl-meta-tyramine

A Simple Histochemical Screening Method for Amine Uptake

“…A number of psychotropic drugs, particularly antidepressants and antiparkinsonian drugs, are considered to exert their pharmacological effects by inhibiting the mechanism of the central NA, 5-HT and DA containing neurons (10,11), although a few clinically effective antidepressants have no such inhibitory effects (12)(13)(14). Because a specific physiological and pathophysiological role has been attributed to each amine and it has been noted that the uptake process of each neuronal system has different sensitivities to various drugs (15)(16)(17), it is important to clarify the selectivity by which a drug inhibits one or more amine uptake mechanism, when applied in vivo. For this purpose, pharmacological, biochemical and histochemical techniques have been used (12,15,(18)(19)(20).…”

“…Because a specific physiological and pathophysiological role has been attributed to each amine and it has been noted that the uptake process of each neuronal system has different sensitivities to various drugs (15)(16)(17), it is important to clarify the selectivity by which a drug inhibits one or more amine uptake mechanism, when applied in vivo. For this purpose, pharmacological, biochemical and histochemical techniques have been used (12,15,(18)(19)(20). The present histochemical technique can also be used for this purpose, because the pattern of action of some imipramine-like drugs obtained in this study was much the same as the pattern obtained by biochemical methods (18,19,(21)(22)(23)(24)(25).…”

Depression in Patients With Epilepsy

“…They are those who have low MHPG in urine; no change in urinary MHPG following treatment with imipramine or desipramine; mood responds to administration of imipramine or desipramine (Bunney et al 1967;Fawcett et al 1972;T1aas et al 1972;Beclanann and Goodwin 1975); an elevation of mood with dexamphetamine (Fawcett et al 1972) and failure to respond to amitriptyline. This is somewhat confusing, as most authors agree that imipramine and desipramine have differential actions on the monoamines: desipramine has a much more marked inhibitory effect on re-uptake of NA into the neurone than on re-uptake of 5HT, while imipramine has a slight but significant effect on NA re-uptake, as well as affecting 5HT (Carlsson et al 1969a;1969b;Renyi 1969). T1aas et al (1972) reported that in those patients who responded to imipramine or desipramine and having the low baseline urinary MHPG level, the MHPG level slightly increased or did not change after 4 weeks of treatment.…”

“…As was described earlier, Group "A" patients with low urinary MHPG do not respond to amitriptyline. It is conceivable that these less favourable results are based on the relatively slight NA-potentiating effect of amitriptyline, while the favourable effect in normal or high MHPG excretors is based on its relatively marked influence on 5HT ( van Praag 1977) • Early reports suggested that clomipramine may owe its clinical efficacy to its ability to inhibit 5HT uptake (Carlsson et al 1969a;Waldmeier 1976). More recently, zimelidine, a selective 5HT re-uptake inhibitor (Ogren et al 1981) has been 0 shown to be antidepressant (Montgomery et al 1981;d'Elia et al 1981;Aberg 1981;w:linder et al 1981).…”

“…Briefly it holds that a central 5HT deficiency may represent a susceptibility or vulnerability to affective illness, and this predisposition may separate the depressive patient from the normal individual: hence, if catecholamine levels decrease, depression occurs (when both catecholamines and indoleamines are low) and if the catecholamines increase, it would be accompanied by mania. Carlsson et al (1969a) suggest, moreover, that blockade of 5HT re-uptake is involved in the mood-elevating action of the TCAs, with the tertiary amines such as amitriptyline being more potent, whereas the blockade of NA re-uptake promotes drive in the depressed patient which is more successfully done by the secondary amines such as desipramine, nortriptyline and protriptyline. Ridges (1975) in her review concludes that most researchers have shown 5HIAA levels to be reduced in depression, (especially in unipolar depressives), whereas equivocal data have been obtained in studies of the catecholamine metabolites.…”