Monoamine oxidase inhibitors 7? -amphetamine

The amphetamines and the anorexiants should not be given during or within 14 days after administration of monoamine oxidase inhibitors (see Chap. 31) because the patient may experience hypertensive crisis and intracranial hemorrhage. When guanethidine is administered with the amphetamines or the anorexiants, the antihypertensive effect of guanethidine may decrease. Coadministration of the amphetamines or the anorexiants with the tricyclic antidepressants may decrease the effects of the amphetamines or the anorexiants. 

The prototype amphetamine enhances release and bloeks reuptake of DA, norepinephrine (ME), and 5-HT and is also a monoamine oxidase inhibitor. As a result of these effeets, drugs in this class are potent indireet agonists at monoaminergie reeeptors. In experimental animals, amphetamine... 

When Schildkraut introduced the monoamine theory of depression, he admitted that there was little direct evidence for it. Instead, it was based on the supposed effectiveness of antidepressant medication and the mistaken belief that reserpine makes people depressed. Schildkraut acknowledged that Most of this evidence is indirect, deriving from pharmacological studies with drugs such as reserpine, amphetamine and the monoamine oxidase inhibitor antidepressants which produce affective changes. 21 A half-century has passed since his chemical-imbalance theory of depression was introduced, and the presumed effectiveness of antidepressants remains the primary evidence in its support. But as we have seen, the therapeutic effects of antidepressants are largely due to the placebo effect, and this pretty much knocks the legs out from under the biochemical theory. 

Clinical success with the monoamine oxidase inhibitor and amphetamine analogue tranylcypromine (27) led to... 

Phentermine (30 mg in the morning or 8 mg before meals) has less powerful stimulant activity and lower abuse potential than amphetamines and was an effective adjunct in placebo-controlled studies. Adverse effects (e.g., increased blood pressure, palpitations, arrhythmias, mydriasis, altered insulin or oral hypoglycemic requirements) and interactions with monoamine oxidase inhibitors have implications for patient selection. 

Amphetamine and cocaine also increase noradrenaline release and a number of drugs with mainly noradrenergic actions can also cause a hyperactive delirium. These include ephedrine, phenylpropanolamine, aminophylline, maprotiline and monoamine oxidase inhibitors (Hollister, 1986). 

Monoamine oxidase inhibitors. The monoamine oxidase inhibitors (MAOIs) inhibit the intracellular catabolic enzyme monoamine oxidase. There are two types of monoamine oxidase MAO-A and MAO-B, both of which metabolize tyramine and dopamine. In addition, MAO-A preferentially metabolizes norepinephrine, epinephrine, and serotonin, and MAO-B preferentially metabolizes phenylethylamine (an endogenous amphetamine-like substance) and N-methylhistamine (Ernst, 1996). Some MAOIs are selective for A or B and some are nonselective (mixed). In addition, irreversible MAOIs (e.g., phenelzine, tranylcypromine) are more susceptible to the cheese effect than are the reversible agents (e.g., moclobemide). 

Nolen WA, Haffmans PMJ, Bouvy PF, et al Monoamine oxidase inhibitors in resistant major depression. J Affect Disord 28 189-197, 1993 Nomikos GC, Damsma G, Wenkstern D, et al Chronic desipramine enhances amphetamine-induced increases in interstitial concentrations of dopamine in the nucleus accumbens. Eur J Pharmacol 195 63-73, 1991 Nomikos GC, Damsma D, Wenkstern D, et al Effects of chronic bupropion on interstitial concentrations of dopamine in rat nucleus accumbens and striatum. Neuropsychopharmacology 7 7-14, 1992... 

A collaborative VA study (364) found that the addition of imipramine or a monoamine oxidase inhibitor to CPZ did not benefit chronic psychotic patients any more than CPZ alone. Further, the addition of an amphetamine was slightly harmful. This finding has since been replicated in several studies on apathetic schizophrenic patients (365). A study of chronic ambulatory schizophrenics compared amitriptyline plus perphenazine with perphenazine alone ( 366). While they found the combination slightly better in ameliorating depressive symptoms, it was at the cost of a slight increase in patients thought disorder. 

EXTENSIONS AND COMMENTARY In the 1960 s there was quite a bit of interest in a couple of pharmaceutical houses with the indole analogues of amphetamine. Both the alpha-methylated tryptamine (this compound, a-MT) and the alpha-ethylated homologue (a-ET, see its separate recipe) were found to be effective monoamine oxidase inhibitors, and both were clinically studied as potential antidepressants. The ethyl compound became a commercial drug, offered by the Upjohn Company as Monase, but now is considered to be without medical use and is a Schedule I drug. It is interesting that this methyl compound, a-MT was also a medically available antidepressant in the Soviet Union in the 1960 s and was sold under the name of Indopan, in 5 and 10 milligram tablets. 

A similar sentiment was expressed in a later British textbook of psychopharmacology Antidepressant drugs, like imipramine and the monoamine oxidase inhibitors differ from euphoriant drugs such as amphetamine in that they appear to act specifically against depressive symptoms (Dally 1967, p. 10). 

Drug interactions The depressant actions of morphine are enhanced by phenothiazines (see p. 127), monoamine oxidase inhibitors (see p.123), and tricyclic antidepressants (see p. 119 and Figure 14.5). Low doses of amphetamine (see p. 103) strangely enhance analgesia. Hydroxyzine (see p. 422) also enhances analgesia. 

The amphetamines should not be used together with or within 14 days of any monoamine oxidase inhibitors severe hypertensive reactions and on occasion confu-sional states (for example with fenfluramine) can occur (SED-9, 9). 

Anorectic drugs, which are structurally related to the amphetamines, act mainly on the satiety centre in the hypothalamus and also increase general physical activity (1). All of them, except fenfluramine, stimulate the central nervous system and can cause restlessness, nervousness, irritabihty, and insomnia. Adverse effects also occur through sympathetic stimulation and gastrointestinal irritation. Drug interactions can occur with monoamine oxidase inhibitors. Dexamfetamine, phenmetrazine, and benzfetamine can cause dependence. Some of them have been associated with cardiac valvulopathy and primary pulmonary hypertension (2). 

MDMA (3.4-methylenedioxymethylamphetamjne EA 1475 XTC Ecstasy E ) has amphetamine-like actions, and induces release of, and is a (re-) uptake inhibitor of 5-hydroxytryptamine. Also, it is a monoamine-oxidase INHIBITOR (MAOI, type A), slowing catabolism of 5-HT. It is a PSYCHOTROPIC AGENT and drug of abuse. 

Monoamine oxidase inhibitors and many pharmacological agents are synergistic, sometimes resulting in a hypertensive crisis. The agents with which the MAOIs may be synergistic include amphetamine, dextroamphetamine, methyl amphetamine, ephedrine, procaine preparations (which usually contain norepinephrine), epinephrine, methyldopa, and phenylpropanolamine (over-the-counter cold preparations). 

Amphetamine [XXII) is a central stimulant and many would not classify it with the antidepressant drugs proper. It has, however, been extensively used in the treatment of depression, it produces euphoria and some at least of its actions may be due to inhibition of monoamine oxidase. However, it also inhibits dopamine- S-oxidase, impairs the noradrenaline binding capacity of the brain and has direct sympathomimetic activity. Its classification with the antidepressants seems, therefore, to be justified, but it is not included with the monoamine oxidase inhibitors, since only a small part of its action can be attributed to enzyme inhibition. Amphetamine is a potentially addictive drug and it should be used cautiously and over short periods of time. Other compounds which are used, if at all, only for the treatment of mild depression, include methylphenidate [XXIII), pipradol [Table 5.2) and deanol (XXIV). The last named compound is interesting since it may owe its effectiveness to a stimulant action on acetylcholine synthesis > . ... 

Drug overdoses involving stimulants (eg, amphetamines, cocaine, phencyclidine, monoamine oxidase inhibitors) or strychnine. 

Metabolic inactivation, whether taking place in the e,r, or at other sites, is often accidentally inhibited by other drugs. Thus many patients have died as a result of the simultaneous administration of an inhibitor of monoamine oxidase (an enzyme present in mitochondria) and an amine drug which is not toxic on its own. These monoamine oxidase inhibitors, such as tranylcypromine 9,47), are prescribed as mood-elevators in depressive illnesses. Until their synergistic properties were realized, they caused many deaths after usually safe doses of amphetamine, pethidine, and amitriptyline, or after the patient had consumed food rich in pressor amines such as tyramine such foods are red wine, meat-extract, yeast-extract, broad beans, and particularly cheese. These are examples of unfortunate synergism, but many favourable cases are known, examples of which will now be given. 

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