Concomitant use of monoamine oxidase inhibitor and tyrosine in parenteral nutrition.

Monoamine oxidase inhibitors (MAOIs) prevent the breakdown of tyramine in the body, and can cause a sudden increase in blood pressure with significant tyramine build up. This phenomenon, when it occurs, is known as tyramine pressor response. It is unknown if tyrosine administered in parenteral nutrition (PN) leads to tyramine build-up with concomitant use of MAOIs. It is also unknown if PN patients who are taking MAOI are at risk for the tyramine pressor response. This is a theoretical possibility as tyrosine endogenously undergoes decarboxylation to produce tyramine. We describe our experience with a 67-year-old woman with severe depression who was on the MAOI, transdermal selegiline. Her clinical course was complicated by an inability to take adequate per oral (PO) intake and she met criteria for unspecified severe protein-calorie-malnutrition in the context of social or environmental circumstances. Therefore, she required PN initiation. PlenamineTM (B. Braun, Bethlehem, PA, USA) was used as the amino acid source in the PN, which contains 39 mg of tyrosine per 100 ml of solution. The patient was monitored closely for any signs of hypertensive crisis while on PN and selegiline. She safely tolerated the combined therapy without any side effects. This is the first documented report of co-administration of PN containing tyrosine along with a MAOI. Our findings suggest that the dose of selegiline used in this patient can be co-administered safely in the setting of PN. However, further study is needed to verify our findings beyond this one patient. In conclusion, we recommend initiating PN and increasing it to goal in patients taking MAOIs, gradually, while monitoring for hypertensive crisis given the theoretical possibility of the tyramine pressor response.

Tyramine exerts hypolipidemic and anti-obesity effects in vivo

Abstract Obesity and dyslipidemia are conditions often associated with cardiovascular risk, inflammation, oxidative stress, and death. Thus, a new approach has been highlighted to promote research and development of pharmacological tools derived from natural sources. Among the most widely studied groups of substances, polyphenols such as tyramine stand out. This study investigated hypolipidemic and anti-obesity properties of tyramine. Oral toxicity evaluation, models of dyslipidemia and obesity were used. To induce dyslipidemia, Poloxamer-407 (P-407) was administered intraperitoneally. In the hypercholesterolemic and obesity model, specific diet and oral tyramine were provided. After 24h of P-407 administration, tyramine 2 mg/kg (T2) decreased triglycerides (TG) (2057.0 ± 158.5 mg/dL vs. 2838 ± 168.3 mg/dL). After 48h, TG were decreased by T2 (453.0 ± 35.47 vs. 760.2 ± 41.86 mg/dL) and 4 mg/kg (T4) (605.8 ± 26.61 760.2 ± 41.86 mg/dL). T2 reduced total cholesterol (TC) after 24h (309.0 ± 11.17 mg/dL vs. 399.7 ± 15.7 mg/dL); After 48h, 1 mg/kg (T1) (220.5 ± 12.78 mg/dL), T2 (205.8 ± 7.1 mg/dL) and T4 (216.8 ± 12.79 mg/dL), compared to P-407 (275.5 ± 12.1 mg/dL). The treatment decreased thiobarbituric acid reactive substances and nitrite in liver, increased superoxide dismutase, reduced the diet-induced dyslipidemia, decreasing TC around 15%. Tyramine reduced body mass, glucose, and TC after hypercaloric feed. Treatment with 5 mg/L (0.46 ± 0.04 ng/dL) and 10 mg/L (0.44 ± 0.02 ng/dL) reduced plasma insulin (1.18 ± 0.23 ng/dL). Tyramine increased adiponectin at 5 mg/L (1.02 ± 0.02 vs. 0.83 ± 0.02 ng/mL) and 10mg/L (0.96 ± 0.04 ng/mL). In conclusion, tyramine has low toxicity in rodents, has antioxidant effect, reduces plasma triglycerides and cholesterol levels. However, further studies should be conducted in rodents and non-rodents to better understand the pharmacodynamic and pharmacokinetic properties of tyramine

Mechanisms of the antilipolytic response of human adipocytes to tyramine, a trace amine present in food

Tyramine is found in foodstuffs, the richest being cheeses, sausages, and wines. Tyramine has been recognized to release catecholamines from nerve endings and to trigger hypertensive reaction. Thereby, tyramine-free diet is recommended for depressed patients treated with irreversible inhibitors of monoamine oxidases (MAO) to limit the risk of hypertension. Tyramine is a substrate of amine oxidases and also an agonist at trace amine-associated receptors. Our aim was to characterize the dose-dependent effects of tyramine on human adipocyte metabolic functions. Lipolytic activity was determined in adipocytes from human subcutaneous abdominal adipose tissue. Glycerol release was increased by a fourfold factor with classical lipolytic agents (1 μM isoprenaline, 1 mM isobutylmethylxanthine) while the amine was ineffective from 0.01 to 100 μM and hardly stimulatory at 1 mM. Tyramine exhibited a partial antilipolytic effect at 100 μM and 1 mM, which was similar to that of insulin but weaker than that obtained with agonists at purinergic A1 receptors, α2-adrenoceptors, or nicotinic acid receptors. Gi-protein blockade by Pertussis toxin abolished all these antilipolytic responses save that of tyramine. Indeed, tyramine antilipolytic effect was impaired by MAO-A inhibition. Tyramine inhibited protein tyrosine phosphatase activities in a manner sensitive to ascorbic acid and amine oxidase inhibitors. Thus, millimolar tyramine restrained lipolysis via the hydrogen peroxide it generates when oxidized by MAO. Since tyramine plasma levels have been reported to reach 0.2 μM after ingestion of 200 mg tyramine in healthy individuals, the direct effects we observed in vitro on adipocytes could be nutritionally relevant only when the MAO-dependent hepato-intestinal detoxifying system is overpassed

Myocardial Injury from Tranylcypromine-Induced Hypertensive Crisis Secondary to Excessive Tyramine Intake.

Monoamine oxidase inhibitors (MAOIs) are known to cause hypertensive crisis when combined with intake of tyramine, classically found in cheese. We present a case of MAOI-induced hypertensive crisis leading to significant troponin release after soft cheese intake. A 51-year-old lady presented with left-sided chest pain, palpitations and headache in the context of significant hypertension after eating soft cheese. She had a similar episode 2 month prior to this presentation, which resulted in a diagnosis of non-ST elevation myocardial infarction after a troponin of 2768 ng/L (Ref < 17 ng/L) with normal cardiac investigations and CT pulmonary angiogram. She was known to be on tranylcypromine for bipolar depression. Subsequent cardiac investigations were normal, as were those for phaeochromocytoma and Conn's disease. Tranylcypromine is a non-selective irreversible MAOI used in refractory depression and bipolar disorder. MAOIs are known to cause hypertensive crisis when combined with soft cheese due to unopposed release of catecholamines from reduced tyramine metabolisation, leading to injury and possible myonecrosis. Three previous case reports have demonstrated either creatinine kinase or troponin rise with myocardial infarction due to this hypertensive crisis and our case is the fourth with significant hypertension and cardiac biomarker rise related to MAOI, specifically tranylcypromine.

Mechanisms of the antilipolytic response of human adipocytes to tyramine, a trace amine present in food.

Tyramine is found in foodstuffs, the richest being cheeses, sausages, and wines. Tyramine has been recognized to release catecholamines from nerve endings and to trigger hypertensive reaction. Thereby, tyramine-free diet is recommended for depressed patients treated with irreversible inhibitors of monoamine oxidases (MAO) to limit the risk of hypertension. Tyramine is a substrate of amine oxidases and also an agonist at trace amine-associated receptors. Our aim was to characterize the dose-dependent effects of tyramine on human adipocyte metabolic functions. Lipolytic activity was determined in adipocytes from human subcutaneous abdominal adipose tissue. Glycerol release was increased by a fourfold factor with classical lipolytic agents (1 µM isoprenaline, 1 mM isobutylmethylxanthine) while the amine was ineffective from 0.01 to 100 µM and hardly stimulatory at 1 mM. Tyramine exhibited a partial antilipolytic effect at 100 µM and 1 mM, which was similar to that of insulin but weaker than that obtained with agonists at purinergic A1 receptors, α2-adrenoceptors, or nicotinic acid receptors. Gi-protein blockade by Pertussis toxin abolished all these antilipolytic responses save that of tyramine. Indeed, tyramine antilipolytic effect was impaired by MAO-A inhibition. Tyramine inhibited protein tyrosine phosphatase activities in a manner sensitive to ascorbic acid and amine oxidase inhibitors. Thus, millimolar tyramine restrained lipolysis via the hydrogen peroxide it generates when oxidized by MAO. Since tyramine plasma levels have been reported to reach 0.2 µM after ingestion of 200 mg tyramine in healthy individuals, the direct effects we observed in vitro on adipocytes could be nutritionally relevant only when the MAO-dependent hepato-intestinal detoxifying system is overpassed.

Development of Tyrosine Decarboxylase-Negative Strains of Lactobacillus curvatus by Classical Strain Improvement.

Biogenic amines have been widely studied because of their potential toxicity in fermented foods. Several lactic acid bacteria have the potential to decarboxylate the amino acid tyrosine to tyramine. In this work, we identified two strains of Lactobacillus curvatus, Lbc1 and Lbc2, endowed with the ability to produce tyramine, a metabolic feature that limits their application in starter cultures for fermented meat. To overcome this limitation, we set out to eliminate tyramine production from L. curvatus strains by using classical strain improvement. About 4,000 mutant isolates of both strains were screened using a colorimetric method, and then potential tyrosine decarboxylase-negative mutants were selected. Firm identification of loss-of-function mutants was performed by analytical determination of tyrosine and tyramine in cultivation medium. Of the 8,000 mutants screened, only one mutant of Lbc1 and two mutants of Lbc2 had completely lost the potential to produce tyramine. Subsequently, one tyrosine decarboxylase-negative mutant of both Lbc1 and Lbc2 was characterized in more detail. DNA sequencing of the Lbc1 mutant tdcA gene disclosed two missense mutations in the promoter distal part of the coding sequence. These two mutations result in two amino acid changes in the encoded tyrosine decarboxylase, Pro87Thr and Ser130Leu, presumably inactivating the enzyme activity. The DNA sequence of the other characterized mutant, derived from strain Lbc2, showed that insertion of a 6-bp fragment at nucleotide position 1348 in the tdc gene is presumably the factor leading to loss of activity. With the successful elimination of the undesirable tyramine-producing phenotype without the use of recombinant DNA technology, these developed L. curvatus mutant strains can be safely used in the dairy industry or in the manufacture of various food products.

Tyramine and histamine risk assessment related to consumption of dry fermented sausages by the Spanish population.

Tyramine and histamine are the main dietary bioactive amines related to acute adverse health effects. Dry fermented sausages can easily accumulate high levels of these hazards and are frequently consumed in Spain. The present work aims to assess the exposure to tyramine and histamine from the consumption of dry fermented sausages by the Spanish population and to assess the risk to suffer acute health effects from this exposure. A probabilistic estimation of the exposure to these hazards was derived combining probability distributions of these amines in dry fermented sausages (n = 474) and their consumption by the Spanish population. The mean dietary exposure to tyramine and histamine was 6.2 and 1.39 mg/meal, respectively. The risk of suffering hypertensive crisis or histamine intoxication by healthy population due to tyramine or histamine intake, respectively, exclusively from dry fermented sausages, can be considered negligible. For individuals under treatment with MAOI drugs, the probability to surpass the safe threshold dose (6 mg/meal) was estimated as 34%. For patients with histamine intolerance, even the presence of this amine in food is not tolerable and it could be estimated that 7000 individuals per million could be at risk to suffer the related symptoms after consuming dry fermented sausages.

High intake of dietary tyramine does not deteriorate glucose handling and does not cause adverse cardiovascular effects in mice.

Tyramine is naturally occurring in food and induces pressor responses. Low-tyramine diets are recommended for patients treated with MAO inhibitors to avoid the fatal hypertensive crisis sadly known as "cheese effect". Hence, tyramine intake is suspected to have toxicological consequences in humans, while its administration to type 1 diabetic rodents has been reported to improve glucose tolerance. We investigated in mice whether prolonged tyramine ingestion could alter glucose homeostasis, insulin sensitivity, adipose tissue physiology or cardiovascular functions. Tyramine was added at 0.04 or 0.14 % in the drinking water since this was estimated to increase by 10- to 40-fold the spontaneous tyramine intake of control mice fed a standard diet. Ten to 12 weeks of such tyramine supplementation did not influence body weight gain, adiposity or food consumption. Both doses (reaching approx. 300 and 1100 µmol tyramine/kg bw/day) decreased nonfasting blood glucose but did not modify glucose tolerance or fasting levels of glucose, insulin or circulating lipids. Blood pressure was not increased in tyramine-drinking mice, while only the higher tested dose moderately increased heart rate without change in its variability. Markers of cardiac tissue injury or oxidative stress remained unaltered, except an increased hydrogen peroxide production in heart preparations. In isolated adipocytes, tyramine inhibited lipolysis similarly in treated and control groups, as did insulin. The lack of serious adverse cardiovascular effects of prolonged tyramine supplementation in normoglycemic mice together with the somewhat insulin-like effects found on adipose cells should lead to reconsider favourably the risk/benefit ratio of the intake of this dietary amine.

Effects of the selective glucocorticoid receptor modulator compound A on bone metabolism and inflammation in male mice with collagen-induced arthritis.

Glucocorticoids (GCs) are potent drugs to treat rheumatoid arthritis but exert adverse skeletal effects. Compound A (CpdA) is a selective GC receptor modulator with an improved risk/benefit profile in mouse models of inflammation and bone loss. Here we tested whether CpdA also exerts bone-sparing effects under proinflammatory circumstances using the collagen-induced arthritis model, a murine model of rheumatoid arthritis. CpdA decreased disease activity, paw swelling, and the paw temperature by 43%, 12%, and 7%, respectively, but was less potent than dexamethasone (DEX), which reduced these parameters by 72%, 22%, and 10%, respectively. Moreover, T cells isolated from CpdA- and DEX-treated animals were less active based on proliferation rates after challenge with type II collagen and produced smaller amounts of interferon-γ and TNF as compared with T cells from PBS-treated mice. Histological assessment of the joints confirmed the weaker potency of CpdA as compared with DEX in preventing infiltration of inflammatory cells, induction of osteoclastogenesis, and destruction of articular cartilage. Due to the lack of GC-susceptible arthritis models, we were not able to fully address the bone-sparing potential of CpdA in inflammatory conditions. Nevertheless, the bone formation marker procollagen type 1 N-terminal peptide, a surrogate marker for GC-mediated suppression of bone formation, was significantly decreased by DEX in arthritic mice but not by CpdA. Our data indicate that CpdA moderately suppresses inflammation, whereas the concurrent effects on bone remain unknown. In light of its narrow therapeutic range, CpdA may be more useful as a molecular tool for dissecting GC actions rather than a therapeutic agent.

Dietary restrictions and drug interactions with monoamine oxidase inhibitors: an update.

Monoamine oxidase inhibitors (MAOIs) are effective treatments for depression that has atypical features or that has failed to respond to other antidepressants. However, MAOIs are underused because clinicians are concerned about dietary and drug interactions with this class of medication. Hypertensive crisis and serotonin syndrome can occur in rare cases due to interactions between MAOIs and foods containing tyramine as well as interactions with serotonergic and sympathomimetic agents. A better understanding of the foods and drugs that can cause adverse reactions, as well as knowledge of newer MAOIs with mechanisms of action and delivery methods that reduce these risks, may help clinicians to consider the use of these medications, when appropriate, in their patients with depression.

The transdermal delivery system of monoamine oxidase inhibitors.

Monoamine oxidase inhibitors (MAOIs) were once widely used as effective treatments for major depressive disorder, particularly for patients with atypical or treatment-resistant depression. Today, MAOIs have largely been replaced by newer antidepressants because of concerns over potential serious side effects due to their mechanism of action. Monoamine oxidase (MAO) is an enzyme that metabolizes serotonin, norepinephrine, and dopamine, the neurotransmitters that are most associated with depression; inhibiting MAO, therefore, makes more of these neurotransmitters available for synaptic action. However, MAO also metabolizes tyramine, a trace amine found in some foods that acts as a sympathomimetic. Allowing excess tyramine to accumulate via MAO inhibition can result in hypertensive crisis due to the release of norepinephrine; therefore, patients taking an MAOI have had to follow dietary restrictions to avoid tyramine-rich foods. Hypertensive crisis may also be precipitated by using MAOIs in conjunction with other drugs that have vasoconstrictive properties, that act as sympathomimetics, or that inhibit the reuptake of norepinephrine. Serotonin syndrome is another serious adverse effect that can potentially occur when using an MAOI with another drug that inhibits the reuptake of serotonin. In this article, the mechanism of action of MAOIs is reviewed, along with that of a newer MAOI formulation that lessens the need for dietary restrictions and has a greater safety and tolerability profile than the older oral formulations.

Safety of selegiline transdermal system in clinical practice: analysis of adverse events from postmarketing exposures.

OBJECTIVE: The objective of this analysis is to present the safety profile of selegiline transdermal system (STS) in clinical practice after US Food and Drug Administration approval by analyzing reported postmarketing adverse events (AEs). METHOD: Deidentified data were obtained on AEs, regardless of causality, as collected and compiled in the pharmaceutical company's adverse event collection systems/databases after the launch of STS in the United States. All reports of hypertensive crisis, suicide attempts, and STS overdoses were carefully examined to independently determine relation of the AE to STS. RESULTS: From April 2006 to October 2010, a total of 3,155 AEs in 1,516 patients were reported (5.2% of the total exposures; N = 29,141), regardless of causality. The most frequently reported categories of AEs were general disorders (no. of AEs = 1,037, 3.6%) and central nervous system (CNS) disorders (no. of AEs = 574, 2.0%). A total of 266 reports (0.9%) were classified as serious AEs; CNS disorders (no. of AEs = 71, 26.7%) and cardiac and vascular disorders (no. of AEs = 44, 16.5%) were most common. There were 13 self-reports of possible hypertensive events or hypertension, although objective clinical data were not submitted in any of these cases. Thirteen drug-drug interactions (0.04%) were reported, and 5 were classified as serious. CONCLUSIONS: The most commonly reported AEs were application site reactions and insomnia. Very few patients reported a hypertensive event, and there were no objectively confirmed reports of hypertensive crisis with food at any STS dose. Therapeutic doses of STS appear to have a safety profile in clinical practice that is consistent with that observed in clinical trials. However, given the relatively modest exposure numbers, continued safety monitoring is recommended.

Tyramine and phenylethylamine biosynthesis by food bacteria.

Tyramine poisoning is caused by the ingestion of food containing high levels of tyramine, a biogenic amine. Any foods containing free tyrosine are subject to tyramine formation if poor sanitation and low quality foods are used or if the food is subject to temperature abuse or extended storage time. Tyramine is generated by decarboxylation of the tyrosine through tyrosine decarboxylase (TDC) enzymes derived from the bacteria present in the food. Bacterial TDC have been only unequivocally identified and characterized in Gram-positive bacteria, especially in lactic acid bacteria. Pyridoxal phosphate (PLP)-dependent TDC encoding genes (tyrDC) appeared flanked by a similar genetic organization in several species of lactic acid bacteria, suggesting a common origin by a single mobile genetic element. Bacterial TDC are also able to decarboxylate phenylalanine to produce phenylethylamine (PEA), another biogenic amine. The molecular knowledge of the genes involved in tyramine production has led to the development of molecular methods for the detection of bacteria able to produce tyramine and PEA. These rapid and simple methods could be used for the analysis of the ability to form tyramine by bacteria in order to evaluate the potential risk of tyramine biosynthesis in food products.

The monoamine oxidase type B inhibitor rasagiline in the treatment of Parkinson disease: is tyramine a challenge?

Rasagiline is an irreversible monoamine oxidase type B (MAO-B) inhibitor indicated for the treatment of the signs and symptoms of idiopathic Parkinson disease as initial monotherapy and as adjunct therapy to levodopa. Pharmacologic inhibition of monoamine oxidase type A (MAO-A), but not MAO-B, poses a risk of the "cheese effect," a hypertensive response to excess dietary tyramine, a biogenic sympathomimetic amine. Tyramine challenge studies, conducted to characterize rasagiline selectivity for the MAO-B enzyme and tyramine sensitivity, demonstrate that rasagiline, when used at the recommended dose, is selective for MAO-B and is not associated with heightened tyramine sensitivity. This conclusion is also supported by safety results from large clinical trials of rasagiline in Parkinson disease involving 2066 rasagiline-treated patients who did not require dietary tyramine restriction per protocol. In late 2009, US labeling for rasagiline was modified to state that dietary tyramine restrictions are not ordinarily required when rasagiline is administered at recommended doses. In addition, because rasagiline has been demonstrated to be selective for MAO-B at the approved dose of up to 1 mg/d, contraindications regarding concomitant use with sympathomimetic amines, use of sympathomimetic vasopressors in conjunction with general or local anesthesia, and use in patients with pheochromocytoma also were removed.

Clinical pharmacology tyramine challenge study to determine the selectivity of the monoamine oxidase type B (MAO-B) inhibitor rasagiline.

Rasagiline is a selective, monoamine oxidase (MAO)-B inhibitor indicated for treatment of Parkinson's disease. This double-blind, placebo-controlled study determined the tyramine sensitivity factor (TSF) and degree of MAO-A inhibition (ie, reduction in plasma dihydroxyphenylglycol) in healthy volunteers who received phenelzine (15 mg, 3 times daily; positive control), selegiline (5 mg, twice daily), or rasagiline (1-6 mg, once daily) for 14 days or rasagiline 2 mg/d for 30 days. The selegiline/rasagiline groups were randomized to placebo or active drug. TSF was highest with phenelzine (17.3) and lowest with placebo (1.5). TSF with selegiline was 2.5. TSFs for rasagiline were as follows: 2.0 for 1 mg/d; 3.3 and 2.4 for 2 mg/d administered for 14 and 30 days, respectively; 4.5 for 4 mg/d; and 5.1 for 6 mg/d. Plasma dihydroxyphenylglycol concentrations suggested that rasagiline 1 mg/d had no effect, whereas rasagiline 2 mg/d had only minimal effect. In contrast, rasagiline 4 and 6 mg/d reduced dihydroxyphenylglycol to a degree approaching that achieved by the positive control phenelzine. Results demonstrate that rasagiline selectively inhibits MAO-B and is not associated with increased tyramine sensitivity at the indicated dose (1 mg/d). These data allowed removal of dietary tyramine restriction from rasagiline US labeling.

Monoamine oxidase inhibitors: a modern guide to an unrequited class of antidepressants.

Monoamine oxidase inhibitors (MAOIs) currently have a "bad rap" and are thus infrequently used in psychopharmacology, even by experienced clinicians. Misinformation about the dietary and drug interactions of MAOIs is widespread, whereas pragmatic tips for utilizing MAOIs to minimize risks and to maximize therapeutic actions are largely lacking in the contemporary literature. While clearly not first-line treatments, MAOIs, in the hands of experienced and well-informed clinicians, can be a powerful therapeutic intervention for patients with depression, panic disorder, and other anxiety disorders who have failed first-line treatments. This article focuses on the pharmacologic mechanisms of MAOIs, since an understanding of these mechanisms may provide a rationale to empower experts to expand their use of these agents. Discussed here are not only the mechanisms of therapeutic action of MAOIs, but also the mechanisms explaining their side effects, including hypertensive interactions with dietary tyramine (so-called "cheese reactions") and drug interactions that can lead to hypertensive reactions with some drugs and serotonin toxicities with others. This article also provides practical tips on how to use MAOIs, including debunking certain myths and giving specific guidance about which foods and drugs to avoid. Those with no previous interest in MAOIs may discover in this article a new "secret weapon" to add to their therapeutic armamentarium for patients who fail to respond to the better-known agents.

Transtelephonic home blood pressure to assess the monoamine oxidase-B inhibitor rasagiline in Parkinson disease.

Monoamine oxidase inhibitors are associated with dietary tyramine interactions that can induce hypertensive crises. Rasagiline mesylate is a novel irreversible selective monoamine oxidase type B inhibitor for Parkinson disease that may have a low risk of interaction with dietary tyramine because of its selectivity. To study interactions of rasagiline with diets unrestricted in tyramine-containing foods, we incorporated transtelephonic, self-monitoring of the blood pressure (BP) into a randomized, placebo-controlled trial of rasagiline 0.5 and 1.0 mg daily in 414 levodopa-treated Parkinson patients with motor fluctuations. The proportion of patients with a systolic BP increase of >30 mm Hg was the primary BP end point. In 13 968 self-measured readings at baseline, the proportion of systolic BP values that increased by >30 mm Hg after a meal ranged from 9.5% to 12.9% in the 3 treatment groups. In 25 733 BPs obtained postrandomization, the proportion of values with a >30-mm Hg systolic postprandial increase was 15% in the placebo group, 15% in the rasagiline 0.5-mg group, and 11% in the rasagiline 1-mg group after 3 weeks of double-blind therapy and 13%, 14%, and 12%, respectively, after 26 weeks of treatment (P value was not significant for all of the comparisons among treatment groups). A postprandial increase in systolic BP to >180 mm Hg at any time after randomization was seen in 3.3%, 2.6%, and 2.9% of the placebo, 0.5-mg, and 1.0-mg rasagiline groups, respectively. These data demonstrate that rasagiline did not induce postprandial hypertension in patients with Parkinson disease who were on an unrestricted diet.