Endogenous depression drugs used

The most frequent and widely used drugs for treating endogenous depression are tricyclic antidepressants. In terms of clinical action they are similar to the phenothiazine... 

A few modifications of the described methods have been suggested for making nortriptyline [27-32], Nortriptyline is a drug with a relatively short latent period of action. It is practically devoid of sedative effects. It is used in manic-depressive psychoses, in all forms of endogenous depression, and also in major depressive conditions. The most common synonyms of nortriptyline are aventyl, nortrilen, motival, vivactil, and pamelor. 

Thymoleptics and thvmeretics are not happy pills , nor are they euphorics. In the case of endogenous depression there is a balancing out of pathological low mood, an effect that is normally obtained in two to three weeks or even longer in many cases. The first effect to become apparent in most cases of depression is the calming one, with the result that anxiousness, unrest and sleep disturbances can be reduced quickly and hence the patient s confidence in the treatment increases. Drugs that may be stimulating or cause euphoria in healthy volunteers, such as amphetamine, alcohol or cocaine, are not suitable for use as antidepressants. 

Viewed as a whole, this investigation supports the view that tricyclic antidepressants are particularly effective in cases of endogenous depression, whereas psychotherapy, possibly in conjunction with drug therapy, constitutes the best solution in cases of situative depression (which would probably be termed reactive depression in the terminology used hitherto). It is interesting to note that the combination of drug therapy with psychotherapy provided additional benefit in patients with endogenous depression. It must, however, be stated that this final conclusion is only based on a fairly small subsample. 

Endogenous biogenic amines in the brain include catecholamines [NE (noradrenaline, NA), dopamine (DA), epinephrine (adrenaline)] 5-HT, histamine, and the so-called trace amines (P-phenylethylamine, tyramine, tryptamine, and octopamine). These amines have in common a arylalkylamine stmcture, and all have been implicated in the etiology of one or more psychiatric disorders and/or in therapeutic and/or adverse effects of drugs used to treat such disorders. In this review on depression, the focus in the case of biogenic amines will be on 5-HT, NE, and DA, although epinephrine and histamine and trace amines have also been implicated (see the section on Other Antidepressant Approaches and Targets ). 

A mechanism for altering synaptic availability of 5-HT is inhibition of presynaptic reaccumulation of neuronally released 5-HT. Selective serotonin reuptake inhibitors (SSRIs e.g., fluoxetine [PROZAC]) potentiate and prolong the action of 5-HT released by neuronal activity. Effects of 5-HT-active drugs, like the SSRIs, in anxiety and depressive disorders strongly suggest an effect of 5-HT in the neurochemical mediation of these disorders. SSRIs are the most widely used treatment for endogenous depression (see Chapter 17). 

Depression is a common condition with both psychologic and physical manifestations. The three major types of depression are (1) reactive depression, a response to external events (2) bipolar affective (manic-depressive) disorder, described in Chapter 29 and (3) major depressive disorder, or endogenous depression, a depression of mood without any obvious medical or situational causes. The drugs used in major depressive disorder are the subject of this chapter. 

Rolipram is a racemic selective inhibitor of cAMP phosphodiesterase that has been used in the treatment of endogenous depression. The R(—)-enantiomer possesses the majority of the therapeutic eflect. After separate administration of the enantiomers by the oral and intravenous routes (Tables 1 and 2), no stereoselectivity appeared in plasma concentrations or in calculated pharmacokinetic [146]. However, it is not known whether this is also true after the administration of the racemate, because enantiomer-enantiomer interactions may affect the enantiomeric plasma concentration ratios of a number of chiral drugs. 

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