Plasma Agmatine Research Articles

Agmatine, telomerase and trace minerals levels in patients with obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) is a disease characterized by repetitive, partially or complete upper airway obstructions resulting in hypoxia and bioelectrical wakefulness reactions along with sleep. There is a limited and different information on the biochemical pathways that may determine harmful effects in OSAS patients with different disease severity. Hence, we aimed to estimate the plasma levels of polyamine agmatine, which has many effects on the central nervous system, telomerase and trace minerals in patients with OSAS. The study included 90 volunteer patients diagnosed with OSAS and divided into three groups of 30 people each according to the apnea-hypopnea index (AHI) score: mild, moderate and severe. Nocturnal blood oxygen saturation percentage (SpO2) and body mass index (BMI) were measured. Plasma agmatine level was defined by ultra-high-pressure liquid chromatography (UHPLC), plasma trace elements (Cu, Co, Mg, Mo, Zn, Se) level by inductively coupled plasma mass spectrometer (ICP-MS) and serum telomerase level by enzyme-linked immunosorbent assay (ELISA) method. It was found that SpO2 value decreased as the disease progressed and showed a negative correlation with BMI, Co and Se plasma levels. The levels of agmatine and telomerase were shown to lower in patients with severe OSAS group compared to other groups. Keywords: agmatine, sleep apnea syndrome, SpO2, telomerase, trace minerals

Agmatine Administration Effects on Equine Gastric Ulceration and Lameness.

Osteoarthritis (OA) accounts for up to 60% of equine lameness. Agmatine, a decarboxylated arginine, may be a viable option for OA management, based on reports of its analgesic properties. Six adult thoroughbred horses, with lameness attributable to thoracic limb OA, received either daily oral phenylbutazone (6.6 mg/kg), agmatine sulfate (25 mg/kg) or a control for 30 days, with 21-day washout periods between treatments. Subjective lameness, thoracic limb ground reaction forces (GRF), plasma agmatine and agmatine metabolite levels were evaluated using an established rubric, a force platform, and mass spectrometry, respectively, before, during and after each treatment period. Gastric ulceration and plasma chemistries were evaluated before and after treatments. Braking GRFs were greater after 14 and 29 days of agmatine compared to phenylbutazone administration. After 14 days of phenylbutazone administration, vertical GRFs were greater than for agmatine or the control. Glandular mucosal ulcer scores were lower after agmatine than phenylbutazone administration. Agmatine plasma levels peaked between 30 and 60 min and were largely undetectable by 24 h after oral administration. In contrast, plasma citric acid levels increased throughout agmatine administration, representing a shift in the metabolomic profile. Agmatine may be a viable option to improve thoracic limb GRFs while reducing the risk of glandular gastric ulceration in horses with OA.

Evaluation of plasma agmatine level and its metabolic pathway in patients with bipolar disorder during manic episode and remission period

Objectives: Agmatine is a cationic amine resulting from the decarboxylation of l-arginine. Agmatine has neuroprotective, anti-inflammatory, anti-stress, and anti-depressant properties. In this study, plasma agmatine, arginine decarboxylase, and agmatinase levels were measured during manic episode and remission period in patients with bipolar disorder.Methods: Thirty healthy volunteers and 30 patients who meet Bipolar Disorder Manic Episode diagnostic criteria were included in the study. Additionally, the changes in the patient group between manic episode and remission period were examined. We evaluated the relationship between levels of l-arginine and arginine decarboxylase in the agmatine synthesis pathway, and level of agmatinase that degrades agmatine.Results: Levels of agmatine and l-arginine were significantly increased than control group during manic episode (p < .01). All parameters were increased during manic episode compared to remission period (p < .05). Agmatinase was significantly decreased both during manic episode (p < .01) and remission period (p < .05) in comparison to the control group. Arginine decarboxylase levels did not show a significant difference between the groups (p > .05).Conclusions: This study indicate that there may be a relationship between bipolar disorder and agmatine and its metabolic pathway. Nonetheless, we believe more comprehensive studies are needed in order to reveal the role of agmatine in etiology of bipolar disorder.Key pointsAgmantine, agmatinase, l-arginine and arginine decarboxylase levels in BD have not been explored before.Various neuro-chemical mechanisms act to increase agmatine in BD; however, agmatine could have elevated to compensate agmatine deficit prior to the manifestation of the disease as in schizophrenia.Elevated agmatine degradation resulting from excess expression of agmatinase which is suggested to be effective in pathogenesis of mood disorders was compensated by this way.Elevated agmatine may be one of the causes which play a role in mania development.Elevated agmatine levels are also suggested to trigger psychosis and be related with the etiology of manic episode and lead to BD.

L-Arginine metabolism before and after 10 weeks of antipsychotic treatment in first-episode psychotic patients

Agmatine is an endogenous NMDA (N-methyl-d-aspartate) antagonist which is synthesized from l-Arginine and described as a novel neurotransmitter. Agmatine is considered to play an important role for the development of schizophrenia. The aim of the present study is to explore the role of agmatine and l-arginine metabolism in medication-naive first-episode psychosis (FEP). We conducted a case control study in medication-naive patients with FEP (n = 40). The healthy volunteers with no family history of schizophrenia (n = 35) matched for age, gender and education level were selected as a control group. The patients were recruited to the study and followed up for 10 weeks. The plasma l-arginine, l-citrulline, l-ornithine and agmatine levels were measured using modified liquid chromatography/mass spectrometry. The plasma levels of l-arginine, l-citrulline and agmatine (p < 0.0001), but not l-ornithine and agmatinase (p > 0.05), were significantly increased during baseline analysis. After 10 weeks of treatment, plasma l-arginine and l-citrulline levels were still significantly increased (p < 0.05) while l-ornithine and agmatinase levels remained unchanged (p > 0.05). Conversely, plasma agmatine levels were significantly decreased after the treatment (p < 0.0001). Positive and negative predictive values of agmatine used for evaluating the diagnostic accuracy were 95.1% and 97.1%, respectively (p < 000.1). This is the first study of arginine metabolism and agmatine in medication-naive first-episode patients and provides evidence of increased levels of an endogenous NMDA antagonist which decreases following antipsychotic treatment.

Decreased plasma agmatine levels in autistic subjects.

Agmatine is a polyamine endogenously synthesized from arginine and is considered to be a new neurotransmitter. Agmatine has been implicated in the pathophysiology of several diseases such as anxiety disorder, depression, and schizophrenia. Agmatine also possesses anticonvulsant, neuroprotective, antiapoptotic, antioxidant, anxiolytic, and antidepressant effects. Furthermore, agmatine inhibits the nitric oxide synthase enzyme and exerts antagonist effects on NMDA, alpha-2, and imidazoline receptors. Considering these characteristics, the present study investigated whether agmatine plays a role in the pathogenesis of autistic spectrum disorders (ASDs). Therefore, plasma agmatine levels were evaluated in 34 patients with ASD and 28 non-ASD controls. Plasma agmatine levels were measured using the HPLC method. The study found remarkably lower agmatine levels in patients with ASD compared with the non-ASD control group (p<0.001). These findings support the notion that agmatine might contribute to the pathogenesis of ASD and may serve as a new target for treatment.

Endogenous Agmatine Induced by Ischemic Preconditioning Regulates Ischemic Tolerance Following Cerebral Ischemia

Ischemic preconditioning (IP) is one of the most important endogenous mechanisms that protect the cells against ischemia-reperfusion (I/R) injury. However, the exact molecular mechanisms remain unclear. In this study, we showed that changes in the level of agmatine were correlated with ischemic tolerance. Changes in brain edema, infarct volume, level of agmatine, and expression of arginine decarboxylase (ADC) and nitric oxide synthases (NOS; inducible NOS [iNOS] and neural NOS [nNOS]) were analyzed during I/R injury with or without IP in the rat brain. After cerebral ischemia, brain edema and infarct volume were significantly reduced in the IP group. The level of agmatine was increased before and during ischemic injury and remained elevated in the early reperfusion phase in the IP group compared to the experimental control (EC) group. During IP, the level of plasma agmatine was increased in the early phase of IP, but that of liver agmatine was abruptly decreased. However, the level of agmatine was definitely increased in the ipsilateral and contralateral hemisphere of brain during the IP. IP also increased the expression of ADC—the enzyme responsible for the synthesis of endogenous agmatine—before, during, and after ischemic injury. In addition, ischemic injury increased endogenous ADC expression in the EC group. The expression of nNOS was reduced in the I/R injured brain in the IP group. These results suggest that endogenous increased agmatine may be a component of the ischemic tolerance response that is induced by IP. Agmatine may have a pivotal role in endogenous ischemic tolerance.

L-Arginine supplementation prevents allodynia and hyperalgesia in painful diabetic neuropathic rats by normalizing plasma nitric oxide concentration and increasing plasma agmatine concentration

Neuropathic pain is a common diabetic complication. It is characterized by symptoms of spontaneous and stimulus-evoked pain including hyperalgesia and allodynia. L-Arginine is a common precursor of many metabolites of biological interest, in particular, nitric oxide (NO), ornithine, and hence polyamines. In central nervous system, NO, glutamate, and polyamines share an N-methyl-D-aspartate (NMDA) receptor-mediated effect. We hypothesized that a variation in arginine metabolism caused by diabetes may contribute to development and maintenance of neuropathic pain and to the worsening of clinical and biological signs of diabetes. We examined whether oral L-arginine supplementation (2.58±0.13g/l in drinking water for 3weeks) could improve the development of neuropathic pain and the clinical, biological, and metabolic complications of diabetes in streptozocin (STZ)-induced diabetic (D) rats. STZ administration induced classical symptoms of type 1 diabetes. Diabetic rats also displayed mechanical hypersensitivity, tactile, and thermal allodynia. Plasma citrulline and NO levels were increased in diabetic hyperalgesic/allodynic rats. L-Arginine supplementation failed to reduce hyperglycaemia, polyphagia, and weight loss. Moreover, it abolished hyperalgesia and allodynia by normalizing NO plasma concentration and increasing plasma agmatine concentration. L-Arginine supplementation prevented the development of mechanical hyperalgesia, tactile, and thermal allodynia in painful diabetic neuropathy with concomitant reduction of NO and increased agmatine production, offering new therapeutic opportunities for the management of diabetic neuropathic pain.

The Effect of Fentanyl Administration on Plasma Agmatine Concentration In Critically Ill Patients

Background: Agmatine, a product of L-arginine metabolism, has been shown to influence opioid tolerance, dependence and withdrawal in animal studies. The purpose of this study was to characterize the plasma agmatine concentration of critically ill, mechanically ventilated patients receiving continuous fentanyl infusion as part of their sedation/analgesia regimen. We hypothesized that these patients would demonstrate lower plasma agmatine levels. Methods: All admissions to our pediatric intensive care unit (PICU) who received mechanical ventilation and fentanyl infusions as part of their sedation/analgesia regimen were eligible. Plasma agmatine concentrations were correlated with patient demographics and medication administration data. Results: Twenty two mechanically ventilated children were enrolled and showed a negative correlation between ? plasma agmatine concentration and the COMFORT score (r=-0.42, p<0.01), ? cumulative fentanyl dose (r=-0.48, p<0.01), ? fentanyl infusion rate (r=-46, p<0.01), and fentanyl infusion duration (r=-37, p<0.01). Conclusions: Mechanically ventilated, critically ill patients receiving prolonged opioid infusions and meeting the definition of tolerance demonstrated lower plasma agmatine concentrations relative to baseline.

Determination of endogenous agmatine in rat plasma by isotope dilution-gas chromatography-mass spectrometry

A method for the determination of endogenous agmatine in rat plasma was developed by isotope dilution-gas chromatography-negative chemical ionization mass spectrometry (GC-NCI/MS). The plasma samples were analyzed after protein precipitation, evaporation, derivatization by hexafluoroacetone (HFAA), and clean-up on a Florisil SPE column. The GC-MS analysis utilized stable isotope d8-agmatine as internal standard. The samples after treatme were tested by negative chemical ionization with selected ion monitoring (SIM) which was set at m/z 492 (molecular ion of agmatine) and m/z 500 (molecular ion of internal standard). The limit of detection (LOD) of agmatine standard solution was 0.005 7 ng/mL. The calibration curve of the agmatine spiked in rat plasma showed a good linear relationship at the range of 1.14-57.0 ng/mL (r = 0.997). The recoveries of agmatine spiked in rat plasma ranged from 92.3% to 109.8%. Inter-day and intra-day precisions were less than 15%. The average concentration level of agmatine in rat plasma was (22 +/- 9) ng/mL, and there was no significant difference between male and female SD rats (p > 0.05). The method is high sensitive and specific, and can be used for the determination of endogenous agmatine in plasma. It provides a strong support for the subsequent research of agmatine.

Increased plasma agmatine levels in patients with schizophrenia

Agmatine is an endogenous substance, synthesized from l-arginine, and it is proposed to be a new neurotransmitter. Preclinical studies indicated that agmatine may have an important role in the pathophysiology of schizophrenia. This study was organized to investigate plasma agmatine in patients with schizophrenia and in healthy controls. Eighteen patients with schizophrenia and 19 healthy individuals constituted the subjects. Agmatine levels in the plasma were measured using the HPLC method. The S100B protein level, which is a peripheral biomarker for brain damage, was also measured using the ELISA method. While plasma levels of agmatine in patients with schizophrenia were significantly increased (p < 0.0001) compared to those of healthy individuals (control), there were no significant changes in the levels of S100B protein (p = 0.660). An ROC (receiver operating characteristic) curve analysis revealed that measuring plasma agmatine levels as a clinical diagnostic test would significantly differentiate between patients with schizophrenia and those in the control group (predictive value: 0.969; p < 0.0001). The predictive value of S100B measurements was not statistically significant (p > 0.05). A multiple regression analysis revealed that the age of the patient and the severity of the illness, as indicated by the PANSS score, significantly contributed the plasma agmatine levels in patients with schizophrenia. These results support the hypothesis that an excess agmatine release is important in the development of schizophrenia. The findings also imply that the plasma agmatine level may be a potential biomarker of schizophrenia.

Amino acid profile of plasma and cerebrospinal fluid in preeclampsia

ObjectivesTo determine patterns in amino acids (arginine, GABA, glutamate and glutamine) and the diamine (agmatine) in plasma and cerebrospinal fluid (CSF) of mild and severe preeclampsia compared to control patients, using capillary zone electrophoresis to generate methods for refining diagnosis and prognosis and shed light on the pathophysiological mechanisms of preeclampsia. Study designThis is an observational case-control study in pregnant women that attended the emergency ward of the University Hospital, Mérida, Venezuela, during the period April, 2009–April 2010. Main outcome measuresMolar concentration of amino acids and diamine in plasma and CSF in control, mild and severe preeclampsia patients. ResultsAn increase in glutamate plasma levels was observed in mild preeclampsia and even higher in severe patients, while a biphasic response occurred in the CSF samples with a significant increment in mild preeclampsia patients and a decrease in severe preeclampsia patients. GABA significantly decreased both in plasma and CSF in mild preeclampsia with a tendency to return to normal levels in severe preeclampsia patients. Arginine CSF and plasma levels decreased in mild preeclampsia patients and even more in severe preeclampsia while agmatine significantly increased in plasma levels with no changes in CSF. ConclusionsThe results are discussed in terms of molecules that could be used as biomarkers of the severity of the disease and the possible involvement of these substances in the pathophysiology of preeclampsia.

Low Levels of Plasma Agmatine in the Metabolic Syndrome

The biophysiology of the amino acid l-arginine has been a field of active research. Agmatine, which is a metabolite of l-arginine, is known to participate in many biophysical reactions, including those in the cardiovascular system. We sought to investigate plasma agmatine levels in human subjects as a potential biomarker for the metabolic syndrome. Agmatine concentration was measured in plasma from 322 elderly participants in the Ansan Geriatric study. The metabolic syndrome was defined according to an Asian modified version of criteria established in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. We observed that the metabolic syndrome was associated with low levels of plasma agmatine concentration. The mean plasma agmatine level in the metabolic syndrome group was lower than that in the non-metabolic syndrome group (79.42 ng/mL vs. 82.44 ng/mL, P = 0.024). Agmatine remained significant within the regression model after adjustment for different covariates (adjusted odds ratio, 0.962; 95% confidence interval, 0.933-0.993). We concluded that plasma agmatine levels were lower in subjects with the metabolic syndrome than in those without the metabolic syndrome.

Detection of Agmatine and Octopamine in Rat Brain and Human Plasma by Microchip Electrophoresis

A microchip electrophoresis method with laser induced fluorescence detection was developed for the detection of agmatine (Agm) and octopamine (Oct). The fluorescent derivatization reagent, fluorescein isothiocyanate was used for precolumn derivatization of Agm and Oct. The sodium dodecyl sulfate (SDS) micelles was employed as pseudostationary phase for the separation of Agm and Oct with other endogenous compounds exist in biological samples. Some parameters including buffer concentration, buffer pH, SDS concentration and separation voltage were investigated in detail. Under the optimum conditions, the separation and determination of Agm and Oct was performed within 40 s. The calibration curves were linear for both Agm and Oct over the concentration range of 1.0 × 10−7 to 4.0 × 10−5 M and 1.5 × 10−7 to 4.5 × 10−5 M, respectively. The detection limits of Agm and Oct (S/N = 3) are 5.0 × 10−8 and 8.0 × 10−8 M, respectively. These values make the method very suitable for the determination of Agm and Oct in rat brain tissue and human plasma as demonstrated in this paper.

Agmatine Levels in the Cerebrospinal Fluid of Normal Human Volunteers

Agmatine is an amine formed by the decarboxylation of l-arginine by the enzyme arginine decarboxylase. The fact that exogenous agmatine modulates morphine analgesia and dependence raises the question of whether the biosynthesis of endogenous agmatine is regulated during chronic pain. As a first step to understand the biological role of agmatine in human neurological and psychiatric conditions, this study was aimed to determine the levels of cerebrospinal fluid (CSF) agmatine in normal individuals. The levels of agmatine in the CSF and blood were measured by high-performance liquid chromatography (HPLC) method. Samples of CSF and blood were collected from a total of 10 participants for this study. The CSF agmatine levels ranged from 24.3 to 54.0 ng/mL, whereas the plasma agmatine levels were from 8.4 to 65.1 ng/mL. The mean values with standard error for blood and CSF agmatine were 33.8 ± 16.6 and 40.4 ± 9.1, respectively. The statistical analysis of these 10 samples indicated no correlation between blood and CSF samples (r = .29); however, removing one outlier improved the correlation (r = .6). From this study, the authors conclude that human CSF agmatine levels can be measured by HPLC with precision and that a possible correlation exists between plasma and CSF agmatine levels. This study provides basis for future studies in human chronic pain conditions.

Regulatory mechanisms underlying agmatine homeostasis in humans

Regulation of agmatine homeostasis has so far only been poorly defined. In the present study, three mechanisms regulating human agmatine homeostasis were investigated. 1) Enzymatic regulation: expression of arginine decarboxylase, diamine oxidase, and ornithine decarboxylase in human colon neoplastic tissue was, at the mRNA level, about 75% and 50% lower and 150% higher, respectively, than in the adjacent normal tissue; expression of agmatinase was unchanged. 2) Bacteria-derived agmatine: ten representative bacteria strains of the human intestinal microbiota considerably differed in agmatine production and its efflux into their surrounding fluid, suggesting that the composition of the intestinal microbiota influences the agmatine availability in the gut lumen for absorption. 3) Regulation of blood plasma agmatine concentration by the human liver: at low concentrations in portal venous blood plasma, agmatine either slightly increased or further decreased in blood plasma through liver passage. Above a threshold of 14 ng/ml agmatine in the portal venous blood plasma, substantial hepatic agmatine removal from blood occurred. Taken together, a perturbation of agmatine homeostasis has been proven to be involved in the regulation of malignant cell proliferation. The amount of agmatine available for absorption, which is an important physiological source of agmatine in the human organism, should differ considerably depending on the composition of the bacterial flora in the chyme since the various species of intestinal bacteria largely differ in their ability to form agmatine. Finally, evidence has been presented that the liver plays a crucial physiological role in the maintenance of agmatine homeostasis in the human organism.

Agmatine crosses the blood-brain barrier.

The question of whether agmatine crosses the blood-brain barrier has not been directly addressed, even though peripheral injection of this compound has produced behavioral responses in drug withdrawal, antidepressant, and anti-anxiety paradigms. Two models were used in this investigation. In the first, mice were injected intraperitoneally (i.p.) with agmatine (10, 50, or 300 mg/kg body weight) or arginine (600 mg/kg). After 1 or 3 hours, the animals were killed under gas anesthesia by perfusing their brains with ice-cold saline, and whole-brain agmatine was measured by HPLC. In parallel studies, a rhesus monkey was injected under gas anesthesia either intravenously (i.v.) with agmatine (30 mg/kg) or arginine (150 mg/kg), or intracerebroventricularly (i.c.v.) with agmatine (0.3 mg/kg i.c.v.). At varying times thereafter, cisterna magna cerebrospinal fluid (CSF) and blood plasma were collected and analyzed for agmatine levels. A rise in mouse brain agmatine was apparent after doses of 50 and 300 mg/kg i.p. Monkey CSF agmatine peaked in parallel with plasma agmatine 15 minutes following intravenous (i.v.) agmatine injection and at one sixth the level of the plasma peak. Monkey CSF agmatine peaked 43 minutes after i.v. arginine injection. The ventricular injection of agmatine resulted in a threefold sustained rise in blood plasma agmatine for at least 24 hours after injection. Therefore, agmatine and its precursor, arginine, cross the blood-brain barrier. CSF agmatine may be newly synthesized from peripherally injected arginine.

Is agmatine an endogenous factor against stress?

Agmatine is an endogenous amine synthesized from the decarboxylation of arginine. A proposed intracellular role of agmatine is to balance the production of polyamines (a promitotic process) and nitric oxide (an inflammatory process). Agmatine is also released from neurons upon depolarization. We previously reported that agmatine concentrations are increased in rat pups' brains shortly after hypoxic-ischemia and in the plasma of depressed patients. Herein, male rats (270-290 g) were divided into four groups receiving different degrees of known stress: 2-hour restraint at 21 degrees C, 4-hour restraint at 21 degrees C, 4-hour restraint at 4 degrees C, and control rats only handled at 21 degrees C. Cortex, cerebellum, medulla, hippocampus, hypothalamus, and blood plasma samples were collected for determination of endogenous agmatine levels. No changes in agmatine levels were detected after 2-hour and 4-hour restraint at room temperature, but concentrations of agmatine were increased in all brain regions except cerebellum after 4-hour restraint in the cold. Plasma agmatine levels (ng/mL) were 6.8 +/- 0.6 in controls versus 58.1 +/- 12.8 in the 4-hour restraint-plus-cold group. Cortical agmatine levels (ng/g wet tissue) were 15.3 +/- 2.4 in controls versus 57.4 +/- 19.6 in the 4-hour restraint-plus-cold group. Therefore, endogenous agmatine was increased in response to cold-restraint stress, possibly as a neuroprotective agent.

Quantitation of agmatine by liquid chromatography with laser-induced fluorescence detection

A high performance liquid chromatography (HPLC) method is described for the determination of agmatine, an endogenous neuromodulator. The method involves pre-column derivatization of the sample with a fluorescent tagging reagent, 7-fluoro-4-nitrobenzoxadiazole (NBD-F). The resulting agmatine derivative is stable and can be readily extracted into ethyl acetate at pH 8.5. The extraction enhances the quantification of low level agmatine because it eliminates chromatographic peaks caused by endogenous amino acids. The HPLC separation is carried out on a C 8 reversed phase column and completed in less than 10 min. With laser-induced fluorescence (LIF) detection, the detection limit is 5×10 −9 M agmatine. Method precision (coefficient of variation) is 5% for agmatine in human plasma at the sub-μM level. This method has been validated by determination of agmatine in biological samples including human plasma and rat brain and stomach tissues.

Imidazoline receptors: possible involvement in the pathophysiology and treatment of depression.

Imidazoline receptors (IR), a novel family of non-adrenergic receptors, are present in brain, especially the limbic system, and platelets among other organs. Their functions include central mediation of blood pressure control and possibly modulation of affective symptomatology. Studies of unipolar depressed patients have revealed consistent up-regulation of the I(1) subtype on the platelet. Treatment with cyclic antidepressants is accompanied by down-regulation in responders. Treatment with the non-cyclic bupropion produced similar findings. Studies of human post-mortem brain show changes in depressed subjects but the protein fragments assessed are of different molecular weights than in the platelet. Plasma agmatine is believed to be a putative endogenous ligand for I receptors. Thus, IR may be useful state markers of affective disorders. Copyright 2001 John Wiley & Sons, Ltd.

Plasma agmatine and platelet imidazoline receptors in depression.

Plasma agmatine concentrations are elevated significantly in depressed patients compared to healthy controls. Treatment with the antidepressant bupropion normalized plasma agmatine levels. Correlational evidence is presented that a change in plasma agmatine levels may lead to similar changes in platelet I1 imidazoline receptors.