C. Raymond Lake

Age-adjusted plasma norepinephrine levels are similar in normotensive and hypertensive subjects.

The sympathetic nervous system has been implicated in the pathogenesis of hypertension because of its role in controlling blood pressure and because many drugs that have been found useful in the tr...

Adverse drug effects attributed to phenylpropanolamine: A review of 142 case reports

Phenylpropanolamine (PPA) is contained in about 106 products, over half of which are available over-the-counter (OTC). Most are cough/cold remedies; nine are OTC diet aids. More than nine million Americans were using OTC diet aids in 1981, making PPA the fifth most used drug in the United States, responsible for over

Hypersensitivity to d-amphetamine several years after early social deprivation in rhesus monkeys

200 million in revenues. The safety of PPA remains controversial. Although most controlled studies indicate minimal pressor effects with recommended doses, adverse drug reactions (ADRs) continue to be documented. Since 1965, 142 ADRs have been reported in 85 studies, 69% of these in North America. Many such cases may go unrecognized. About two thirds of all ADRs occurred in females and in patients under 30. Of ADRs attributed to legitimately sold PPA products, 85% occurred after consumption of OTC products versus only 15% after prescription drugs. The PPA product often contained combination ingredients, or PPA was consumed along with additional drugs. An overdose of PPA was taken in about a third of the cases. After ingestion of non-overdose amounts, 82% of the ADRs were severe. The most frequent side effects involved symptoms compatible with acute hypertension, with severe headache the most common complaint. Twenty-four intracranial hemorrhages, eight seizures, and eight deaths (most due to stroke) were associated with PPA ingestion. We have summarized these data in an effort to alert clinicians to the prevalence of usage of PPA products and the potential for adverse effects. In patients who present with elevated blood pressure or signs of acute hypertension, especially hypertensive encephalopathy of undetermined origin, we recommend inquiry about recent ingestion of PPA-containing diet aids and cough/cold products and suggest having such patients remain upright rather than supine.

Gilles de la Tourette's syndrome Clinical, genetic, psychologic, and biochemical aspects in 21 selected families

Social deprivation of rhesus monkeys in infancy results in increased sensitivity to psychotic-like behavioral effects of low doses of d-amphetamine given 2–3 years later. These behavioral effects are associated with increased levels of CSF norepinephrine. These data suggest that social developmental factors could be partially responsible for variation in neurochemical responses and long-lasting differential sensitivity of primates to the psychosis-inducing effects of d-amphetamine.

Deficient Sympathetic Nervous Response in Familial Dysautonomia

Eighty-one patients and relatives with Tourettes syndrome, members of 21 selected families, participated in a 1-day clinic. In 12 of the 13 Jewish families and six of the eight non-Jewish families, there were multiple members with motor and vocal tics by observation or history. Males predominated among those with persistent symptoms, but among those with spontaneous clearing, females predominated. Twelve propositi had troublesome sexual and aggressive impulses, differing only quantitatively from normal. No evidence of abnormality was found in plasma dopamine beta hydroxylase, or norepinephrine levels.

Cerebrospinal fluid measures of neurotransmitter changes associated with pharmacological alteration of the despair response to social separation in rhesus monkeys

Norepinephrine concentration and dopamine-beta-hydroxylase activity were measured in the plasma of 10 dysautonomic patients and 10 normal subjects while they were reclining, standing and exercising. While reclining, dysautonomic patients had normal norepinephrine concentrations and blood pressure, but after standing they did not have a normal increase in their levels of norepinephrine (P less than 0.005), dopamine-beta-hydroxylase (P less than 0.05) or plasma protein concentration (P less than 0.01); they became hypotensive. In reclining dysautonomic patients there appeared to be a correlation between blood pressure and plasma norepinephrine concentration. These data support the view that hypertension and hypotension in dysautonomia are related to the rate of norepinephrine release.

Hydrochlorothiazide‐induced sympathetic hyperactivity in hypertensive patients

Social separation is a risk factor for major depressions that can be modeled in nonhuman primates. Changes in central monoamine neurotransmission are also likely to be involved in major depression. This study examined the relationship between separation-induced depressive-like behavior and central monoamine neurotransmitter changes in rhesus monkeys. Measures of cerebrospinal fluid (CSF) norepinephrine (NE), 5-hydroxyindoleacetic acid (5HIAA), and homovanillic acid (HVA) were used to assess the neurobiological impact of social separation and drug treatments alone or in combination. alpha-Methyl-p-tyrosine exacerbated, and fusaric acid ameliorated, the depressive-like response to separation. Probenecid-induced accumulations of HVA and 5HIAA reflected changes in behavior, but were not consistently affected by drug treatment. In contrast, pretreatment CSF NE was comparatively stable across repeated sampling, and drug-induced changes in this measure were correlated with changes in behavior. Low CSF NE, whether drug-induced or naturally occurring, was associated with a more severe depressive-like response to separation.

Dopamine- -Hydroxylase: Basic and Clinical Studies

Hydrochlorothiazide‐induced diuresis and natriuresis is considered to be responsible for the antihypertensive effect of this drug. After short‐term treatment there is decreased cardiac output and increased peripheral resistance which we have found to be attended by increased plasma norepinephrine (NE) levels. After longer treatment cardiac output returns to normal and peripheral resistance declines. At this time, plasma NE levels remain elevated, indicating that peripheral resistance reduction is not a consequence of a reduction of the elevated level of sympathetic activity. These results provide a rationale for the combined use of diuretics and drugs which diminish noradrenergic activity in the treatment of hypertension.

Altered norepinephrine metabolism following long-term weight recovery in patients with anorexia nervosa

: Dopamine-beta-hydroxylase, the enzyme responsible for conversion of dopamine to norepinephrine, is released along with catecholamines from the adrenal medulla and from sympathetic nerve endings. The properties and mechanisms of the enzymes action are discussed and its distribution described. Dopamine-beta-hydroxylase is a valuable indicator of exocytosis as a mechanism for neurotransmitter release. The enzyme is present in plasma, but its levels vary widely between individuals. This variation seems to be related more to genetic factors than to sympathetic nerve activity. Abnormally high or low plasma levels are associated with several diseases. However, the relation of these levels to disease pathogenesis rather than to genetic determinants is unclear. Levels of the enzyme are elevated in patients with pheochromocytoma and decline after removal of the tumor. Dopamine-beta-hydroxylase levels seem to be normal in hypertensive patients. Inhibition of dopamine-beta-hydroxylase provides a useful pharmacologic approach to evaluating the role of norepinephrine in psychiatric disorders.

The circadian variation of catecholamine metabolism in the subhuman primate.

This study evaluated the relationship between noradrenergic function and long-term weight recovery in patients with anorexia nervosa. Eleven patients with long-term weight maintenance (6 to 72 months) had lower plasma and cerebrospinal fluid concentrations of norepinephrine and 3-methoxy-4-hydroxy-phenylglycol than did healthy controls. Reduced noradrenergic activity may be associated with long-term stability of weight recovery in patients with anorexia nervosa.