Monoamine oxidase inhibitors and atypical antidepressants.

The following conclusions may be drawn from this article: 1. The age at which subjects are considered "elderly" or "geriatric" varies from study to study. By convention, age 65 is usually taken as the minimum age, yet virtually all studies cited included subjects below 65. Indeed, in a majority of studies, most of the subjects were below the conventional age of 65. Defining the minimum age for geriatric psychopharmacology studies is particularly important because there may be considerable pharmacodynamic and pharmacokinetic heterogeneity in people aged 65 and older. Clinical experience suggests that patients below age 80 tend to respond to medications like late middle-age adults, whereas those above age 80, as a group, are more sensitive to drugs. Because people 80 and above constitute the fastest growing group of Americans, it is essential to conduct more therapeutic clinical trials using them as research subjects. Information gathered from persons aged 60 to 79 may not be relevant to this older age group. 2. The total number of individuals studied in carefully controlled, double-blind research studies of MAOIs, atypical antidepressants, or psychomotor stimulants are relatively few when compared with the number of individuals studied with tricyclic antidepressants, or the number of nonelderly subjects studied. 3. Although many older persons are included in mixed-age research populations, the number of studies specifically designed in the elderly is also remarkably few. 4. In those studies that did focus on older patients, the definition of elderly was extended "downward" to include patients at age 55, or even 50. Whether or not this was done in order to enhance research subject recruitment, the net result is to vitiate any overall conclusion regarding the efficacy of drugs in patients over age 65, the usual lower cutoff for "elderly" or "geriatric" definition. 5. With the exception of a handful of patients receiving fluoxetine and methylphenidate, virtually no research patient above the age of 80 has been studied using any of the compounds discussed in this article. 6. Some of the double-blind studies reviewed are more than a decade old and techniques in research design have changed substantially since those studies were conducted. Many of the earlier studies would not be acceptable according to contemporary research design criteria because of inappropriate or inadequate inclusion criteria, inappropriate or inadequate outcome criteria, and inappropriate or inaccurate diagnostic criteria.(ABSTRACT TRUNCATED AT 400 WORDS)     

Monoamine oxidase and catechol-o-methyltransferase activity in hamster and rat insulinomas

Hamster and rat insulinomas were assayed for norepinephrine, dopamine and serotonin concentration and for monoamine oxidase and catechol-o-ethyltransferase (COMT) activity. The concentration of norepinephrine (mean 0.55 mumol/kg, range less than 0.20 to 2.64 mumol/kg) and serotonin (mean 5.22 mucol/kg, rang less than 0.6 to 26.5 mumol/kg) in hamster insulinomas were comparable to previously reported concentrations. Dopamine conentration (mean 0.34 mumol/kg, range less than 0.20 to 0.95 mumol/kg) was only 2 to 2.5% of that reported previously. Monoamine oxidase activity of the hamster and rat insulinomas were comparable to those of normal hamster islets. In contrast, the COMT activity of both insulinomas was much greater than the COMT activity of normal pancreatic islets of both species and was greater than in several other tissues and tumours. The tumour COMT, which was predominantly in the cytosol, was Mg2+ dependent and had a comparable sensitivity to inhibition by tropolone as purified beef-liver COMT. Hamster insulinoma monoamine oxidase was more sensitive than rat insulinoma monoamine oxidase to inhibition by tranylcypromine and deprenyl, while rat insulinoma monoamine oxidase was more sensitive to inhibition by clorgyline and was more heat labile.     

The use of monoamine oxidase inhibitors as adjuncts in the treatment of hypertension and angina pectoris

The newer monoamine oxidase inhibitors have clinical actions in hypertension and angina pectoris similar to those of iproniazid but appear to produce less frequent side effects. Some of the side effects suggest that in addition to amine oxidase inhibition, they may also have a ganglionic blocking action.

The amine oxidase inhibitors are effective and useful in the clinical management of refractory cases of angina pectoris even though they may not alter the electrocardiogram significantly. Since the relief of chest pain also is accompanied frequently by a sense of well-being, cautioning the patient against over-exertion is advisable. Some of the amine oxidase inhibitors are also worthy of a trial in resistant cases of hypertension. However, they should be employed cautiously in these selected cases since their long term effects, even in moderate dosage, on liver and cardiac function are not known.     

Biochemistry of monoamine oxidase inhibitors

The diverse biochemical and pharmacologie actions of the monoamine oxidase inhibitors have proved of great value in learning more of the importance of amines in the body. Investigations with these drugs have revealed the possible involvement of various amines in brain function and in the actions of these and other drugs on brain excitability and regulation of the cardiovascular system.     

Monoamine oxidase: an important intracellular regulator of gastrin release in the rat

The role of monoamine oxidase (MAO) in the meal-induced or amino acid-induced release of gastrin was investigated. Rats that were pretreated with the nonspecific MAO inhibitor nialamide (200 mg/kg) showed a greater rise in meal-induced serum gastrin than did untreated controls. In vitro experiments demonstrated that gastrin secretion from dispersed antral G cells in response to a stimulatory dose of phenylalanine or methylbenzylamine (10 mM) was markedly enhanced if the cells were treated with nialamide. Studies with the more specific MAO inhibitors clorgyline and deprenyl indicated that antral mucosa contained predominantly type A activity. Inhibition of MAO type A with clorgyline, both in vivo and in vitro, resulted in a greater release of gastrin after stimulation by a meal or phenylalanine. It is concluded that MAO may play an important role in the regulation of gastrin release from the G cell by partially controlling the level of amines within the cell.     

Monoamine oxidase and acetylcholinesterase in the neurohypophysis of the hagfish, Eptatretus burgeri

The peripheral region of both dorsal and ventral walls of the neurohypophyseal sac of the hagfish, Eptatretus burgeri, showed strong monoamine oxidase (MAO) activity. Acetylcholinesterase (AChE) activity was detected only in the dorsal wall anterior to the infundibular stalk and in the ventral wall, except for the ependymal cells. AChE was not detected in the dorsal wall posterior to the stalk, where aldehyde-fuchsin-positive material is deposited. From these distribution patterns of MAO and AChE the identity of the structural specializations of the neurohypophysis are discussed as compared with distributions of MAO and AChE in the median eminence and the pars nervosa of higher vertebrates.     

ACE inhibitors in renovascular hypertension

Summary ACE inhibition has provided many insights into the etiology and treatment of renovascular hypertension. Not only have studies using these agents profoundly expanded our understanding of the mechanisms governing preservation of renal perfusion pressures and function beyond arterial lesions, they have provided tools for more precise diagnosis and therapy in clinical practice. ACE inhibitors must be considered the agents of choice for the treatment of renovascular hypertension and provide an effective and safe medical alternative for many patients developing atherosclerotic renovascular lesions with an otherwise unacceptable risk for revascularization procedures. With the advent of widespread clinical use of these agents, however, come many new questions regarding the long-term fate of the kidney beyond vascular lesions and the need for preservation of renal function.     

Monoamine oxidase A gene (MAOA) predicts behavioral aggression following provocation

Monoamine oxidase A gene (MAOA) has earned the nickname “warrior gene” because it has been linked to aggression in observational and survey-based studies. However, no controlled experimental studies have tested whether the warrior gene actually drives behavioral manifestations of these tendencies. We report an experiment, synthesizing work in psychology and behavioral economics, which demonstrates that aggression occurs with greater intensity and frequency as provocation is experimentally manipulated upwards, especially among low activity MAOA (MAOA-L) subjects. In this study, subjects paid to punish those they believed had taken money from them by administering varying amounts of unpleasantly hot (spicy) sauce to their opponent. There is some evidence of a main effect for genotype and some evidence for a gene by environment interaction, such that MAOA is less associated with the occurrence of aggression in a low provocation condition, but significantly predicts such behavior in a high provocation situation. This new evidence for genetic influences on aggression and punishment behavior complicates characterizations of humans as “altruistic” punishers and supports theories of cooperation that propose mixed strategies in the population. It also suggests important implications for the role of individual variance in genetic factors contributing to everyday behaviors and decisions.