Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “TYRAMINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,423 records · Page 79Linked to original sources

Involvement of alpha1B-adrenoceptors in the positive inotropic effect of endogenous noradrenaline in rabbit myocardium.

We studied the alpha1-adrenoceptor subtypes mediating the positive inotropic effects of phenylephrine and noradrenaline as well as endogenous noradrenaline released by tyramine in rabbit papillary muscle. In the presence of propranolol, both phenylephrine and tyramine produced a positive inotropic effect in a concentration-dependent manner. WB4101 (N-[2-(2,6-dimethoxyphenoxy]ethyl]-2,3-dihydro-1,4-benzodioxin+ ++-2-methanamine) and chlorethylclonidine each antagonized the positive inotropic effect of phenylephrine. On the other hand, only chlorethylclonidine significantly blocked the positive inotropic effect of tyramine. However, the presence of both antagonists was needed to block the positive inotropic effect elicited by the exogenous addition of the low concentration of noradrenaline. These data suggest that after extensive blockade of beta-adrenoceptors the positive inotropic effects of phenylephrine and exogenous noradrenaline result from stimulation of the alpha1A- and alpha1B-adrenoceptor subtypes, whereas that of endogenous noradrenaline is mediated via the alpha1B-adrenoceptor subtype. This could be explained by assuming that the alpha1B-adrenoceptor subtype population may be located on a space confronting more closely to the sympathetic nerve endings than the alpha1A-adrenoceptor subtype population.

Adrenergic alpha-Agonists↗

Role of dopamine in behavioral effects of serotonin microinjected into rat striatum.

Bilateral local microinfusion of serotonin (5-hydroxytryptamine; 5-HT) into the ventrolateral striatum (VLS) of the rat forebrain induces quantifiable stereotyped orofacial behaviors. The role of presynaptic dopamine (DA) and structural requirements of indoles for expression of this behavioral effect and for inhibition of neuronal transport of [3H]DA were examined. Bilateral local injection of 6-OHDA (8 micrograms/side) into VLS depleted DA and markedly diminished the behavioral effects of 5-HT. Intracerebral pretreatment with the potent DA transport inhibitors GBR-12909 (6 micrograms/side) or nomifensine (4 micrograms/side) also markedly decreased behavioral responses to 5-HT. A series of indoles and tyramine were examined for ability to induce stereotypy following infusion into the VLS. Of compounds tested, only p-tyramine, 5-HT, tryptamine and L-5-hydroxytryptophan (5-HTP) elicited strong orofacial behaviors; indoles lacking a free amino group or containing other substituents were virtually inactive in vivo, and the effect of 5-HTP was prevented by systemic pretreatment with the decarboxylase inhibitor NSD-1015, indicating its required conversion to 5-HT. Uptake of [3H]DA (0.1 microM) into rat striatal synaptosomes was inhibited in a concentration-dependent manner in the following apparent rank-order: p-tyramine, N-methyl-5-HT, tryptamine, 5-HT, N-methyltryptamine (IC50 = 44-718 nM), other indoles (IC50 = 10-100 microM). These results support the conclusion that oral stereotypy induced by microinjection of 5-HT or other aromatic amines into rat VLS is mediated by local release of endogenous DA. These results extend previous findings indicating that this effect of 5-HT was not blocked by 5-HT receptor antagonists, and suggest mediation by a neuronal transport process involved in the uptake or storage of DA.

Animals↗

Is there an increase in monoamine-oxidase activity in depressive illness?

In a group of depressed patients who had either been treated with or considered suitable for monoamine oxidase (M.A.O.) inhibitor therapy, a highly significant decrease in conjugated tyramine output was observed after an oral tyramine load compared with normal controls. However, there was no difference in conjugated isoprenaline output between the two groups after isoprenaline ingestion, even though this amine is almost solely metabolised by what is likely to be the same conjugation mechanism. Whilst some explanation in terms of altered gut motility is conceivable, it seems more likely that the apparent deficit in tyramine conjugation in depression represents an increase in functional M.A.O. activity. Consequently, this enzyme would metabolise a greater proportion of available amine, causing a proportionately large decrease in the smaller conjugate pool.

Administration, Oral↗

Bovril and moclobemide: a novel therapeutic strategy for central autonomic failure.

The consumption of tyramine-containing foods is contraindicated in patients on classic monoamine oxidase (MAO) inhibitors. We report successful therapeutic use of moclobemide (a MAO-A selective inhibitor) plus controlled amounts of Bovril (a tyramine-rich yeast-extract available as a food) in a patient with pure central autonomic failure who was rendered bed-bound by severe postural hypotension. Standing blood pressure is now at least 90/45 mm Hg. The selectivity of moclobemide allows about a tenth of ingested tyramine to reach nerve endings and thus the modest hypertensive effect of this combination re-established day-to-day function by restoring normotension.

Activities of Daily Living↗

Clinical pharmacology of befloxatone: a brief review.

Clinical pharmacology studies of befloxatone, a new selective reversible inhibitor of monoamine oxidase-A (MAO-A), have addressed safety, with special emphasis on tyramine interactions, and have also investigated pharmacokinetics (PK) and pharmacodynamics in terms of both MAO-A inhibition (using 3,4-dihydroxyphenylglycol, DHPG, as a pharmacological activity marker) and effects on psychomotor and cognitive function, in young and elderly healthy volunteers. Clinical and laboratory safety data were satisfactory in healthy volunteers given single doses of up to 160 mg or repeated doses of up to 80 mg/day for 7 days. Tyramine interaction studies showed that the expected potentiation of the tyramine pressor effect occurred with a safety margin that was so wide as to make dietary restrictions unnecessary with dosages of up to 20 mg once daily in clinical settings. Absorption was rapid (tmax = 2 h), terminal halflife was about 11 h, and PK parameters increased linearly with the dose. Befloxatone induced a dose-dependent decrease in plasma DHPG levels from 2.5 mg upwards, and a 10-mg dose provided sub-maximal activity (80% DHPG decrease) of 24 h duration. No sedative or stimulant effects were detected using several batteries of psychometric tests. Befloxatone was devoid of deleterious effects on memory in young volunteers, and exhibited the EEG profile of a non-sedative antidepressant. In summary, available clinical pharmacology studies confirm that befloxatone is a safe and potent RIMA with no potential for inducing deleterious CNS effects.

Adult↗

Effect of added proteinases and level of starter culture on the formation of biogenic amines in raw milk Manchego cheese.

The influence of two proteinases (Bacillus subtilis neutral proteinase and Micrococcus sp. cysteine proteinase) and two starter culture levels (0.1% and 1%) on biogenic amine formation has been studied in raw ewes' milk Manchego cheese. Amino acid decarboxylating micro-organisms were determined on tyrosine enriched selective media. Biogenic amines were analysed by capillary electrophoresis in citrate buffer at pH 3.6. Addition of proteinases and level of starter culture did not influence the population of micro-organisms with amino acid decarboxylating activity, which represented on average 1% of the bacterial population in 30-day-old cheeses. Tyramine and histamine were detected in all batches of cheese from day 30. Concentrations of tyramine and histamine were higher in cheeses made from milk with neutral proteinase (up to 356 and 284 mg kg(-1), respectively, after 90 days) than in cheeses made from milk with cysteine proteinase (up to 269 and 189 mg kg(-1), respectively) or with no proteinase added (up to 305 and 226 mg kg(-1), respectively). Formation of tyramine and histamine was also favoured in cheeses made with 1% starter culture with respect to cheeses made with only 0.1% starter culture, probably due to the higher pH values of the former cheeses. After 90 days of ripening, concentrations of 10-20 mg kg(-1) phenylethylamine were observed in 9 of the 12 batches, and levels < 10 mg kg(-1) tryptamine were only detected in 3 batches, with no significant relationship between the concentration of these amines and proteinase addition or level of starter culture.

Animals↗

Improved screening procedure for biogenic amine production by lactic acid bacteria.

An improved screening plate method for the detection of amino acid decarboxylase-positive microorganisms (especially lactic acid bacteria) was developed. The suitability and detection level of the designed medium were quantitatively evaluated by confirmation of amine-forming capacity using an HPLC procedure. The potential to produce the biogenic amines (BA) tyramine, histamine, putrescine, and cadaverine, was investigated in a wide number of lactic acid bacteria (LAB) of different origin, including starter cultures, protective cultures, type strains and strains isolated from different food products. Also, several strains of Enterobacteriaceae were examined. Modifications to previously described methods included lowering glucose and sodium chloride concentrations, and increasing the buffer effect with calcium carbonate and potassium phosphate. In addition, pyridoxal-5-phosphate was included as a codecarboxylase factor for its enhancing effect on the amino acid decarboxylase activity. The screening plate method showed a good correlation with the chemical analysis and due to its simplicity it is presented as a suitable and sensitive method to investigate the capacity of biogenic amine production by LAB. Tyramine was the main amine formed by the LAB strains investigated. Enterococci, carnobacteria and some strains of lactobacilli, particularly of Lb. curvatus. Lb. brevis and Lb. buchneri, were the most intensive tyramine formers. Several strains of lactobacilli, Leuconostoc spp., Weissella spp. and pediococci did not show any potential to produce amines. Enterobacteriaceae were associated with cadaverine and putrescine formation. No significant histamine production could be detected for any of the strains tested.

Aromatic-L-Amino-Acid Decarboxylases↗

Differential physiological effects of a low dose and high doses of venlafaxine in major depression.

Venlafaxine is an antidepressant drug with demonstrated serotonin (5-HT) and norepinephrine (NE) reuptake blockade properties in electrophysiological and microdialysis experiments in laboratory animals. In healthy volunteers, its 5-HT reuptake-inhibiting potential has also been clearly documented, but not its NE reuptake blockade action. This double-blind study compared the effects of a low dose (75 mg) and of a forced titration of high (up to 375 mg in 1 wk) daily doses of venlafaxine. Forty-four patients with major depression according to DSM-IV criteria were assessed bi-weekly for the first 2 wk and weekly for the next 2 wk. Inhibition of 5-HT reuptake was estimated using the depletion of whole-blood 5-HT, while that of NE was assessed using the attenuation of the systolic blood-pressure elevations produced by intravenous injections of tyramine. Forty-two patients completed the study. Both the low and the high doses of venlafaxine decreased the levels of 5-HT to the same extent: the reduction was of about 55% after 1 wk and of 75% after 4 wk. The 75 mg/d dose of venlafaxine did not alter the tyramine pressor response, whereas, in patients receiving the higher regimens of venlafaxine, there was a significant attenuation of the pressor effect of tyramine. There was no significant difference between the two treatment arms regarding the modifications of the depression scores. The present data showed that, at its minimal effective dose in depression (75 mg/d), venlafaxine acted as a selective 5-HT reuptake inhibitor, whereas when administered at higher doses (225 and 375 mg/d), it acted as a dual 5-HT and NE reuptake inhibitor.

Adrenergic Uptake Inhibitors↗

Structure and action of heteronemertine polypeptide toxins. Membrane penetration by Cerebratulus lacteus toxin A-III.

The heteronemertine worm Cerebratulus lacteus produces a family of three structurally homologous proteins that function as direct lytic factors for a variety of cells [Kem, W. R., & Blumenthal, K. M. (1978) J. Biol. Chem. 253, 5752-5757]. It is demonstrated herein that the hemolytic activity of the most abundant variant, designated toxin A-III, is unaffected by either extensive iodination or complete blockage of carboxylate groups by tyramine or glycine ethyl ester. Iodination of A-III with lactoperoxidase produced a derivative that is preferentially labeled at His-67 and to a lesat the hemolytic activity of the most abundant variant, designated toxin A-III, is unaffected by either extensive iodination or complete blockage of carboxylate groups by tyramine or glycine ethyl ester. Iodination of A-III with lactoperoxidase produced a derivative that is preferentially labeled at His-67 and to a lesat the hemolytic activity of the most abundant variant, designated toxin A-III, is unaffected by either extensive iodination or complete blockage of carboxylate groups by tyramine or glycine ethyl ester. Iodination of A-III with lactoperoxidase produced a derivative that is preferentially labeled at His-67 and to a lesser extent at Tyr-6. The ratio of labeling at these two positions is approximately 3 to 1. Iodinated A-III is completely insoluble in 10% C13CCOOH. However, following treatment with trypsin-containing liposomes, 15% of the input counts are converted to a Cl3CCOOH-soluble form. Incubation with free trypsin in the presence of liposomes containing N alpha-tosyl-L-lysine chloromethyl ketone results in approximately 60% of the input counts becoming C13CCOOH soluble. Free trypsin renders toxin A-III 90% soluble in 10% C1CCOOH. Electrophoretic analysis of the labeled tryptic peptides generated in the presence of liposomes shows that internal trypsin hydrolyzed the Arg-13-Ser-14 bond, generating exclusively peptide T-1 (residues 1-13) while external trypsin produces peptide T-11 (residues 60-71) as the major radioactive product. These data are consistent with insertion of at least the amino-terminal 13 residues of A-III into the liposome and imply that membrane penetration by this protein may be important for its cytolytic activity.

Chemical Phenomena↗

Inactivation of dopamine beta-hydroxylase by beta-ethynyltyramine: kinetic characterization and covalent modification of an active site peptide.

beta-Ethynyltyramine has been shown to be a potent, mechanism-based inhibitor of dopamine beta-hydroxylase (DBH). This is evidenced by pseudo-first-order, time-dependent inactivation of enzyme, a dependence of inactivation on the presence of ascorbate and oxygen cosubstrates, the ability of tyramine (substrate) and 1-(3,5-difluoro-4-hydroxybenzyl)imidazole-2-thione (competitive multisubstrate inhibitor) to protect against inactivation, and a high affinity of beta-ethynyltyramine for enzyme. Inactivation of DBH by beta-ethynyltyramine is accompanied by stoichiometric, covalent modification of the enzyme. Analysis of the tryptic map following inactivation by [3H]-beta-ethynyltyramine reveals that the radiolabel is associated with a single, 25 amino acid peptide. The sequence of the modified peptide is shown to be Cys-Thr-Gln-Leu-Ala-Leu-Pro-Ala-Ser-Gly-Ile-His-Ile-Phe-Ala-Ser-Gln-Leu- His*- Thr-His-Leu-Thr-Gly-Arg, where His* corresponds to a covalently modified histidine residue. In studies using the separated enantiomers of beta-ethynyltyramine, we have found the R enantiomer to be a reversible, competitive inhibitor versus tyramine substrate with a Ki of 7.9 +/- 0.3 microM. The S enantiomer, while also being a competitive inhibitor (Ki = 33.9 +/- 1.4 microM), is hydroxylated by DBH to give the expected beta-ethynyloctopamine product and also efficiently inactivates the enzyme [kinact(app) = 0.18 +/- 0.02 min-1; KI(app) = 57 +/- 8 microM]. The partition ratio for this process is very low and has been estimated to be about 2.5. This establishes an approximate value for kcat of 0.45 min(-1) and reveals that (S)-beta-ethynyltyramine undergoes a slow turnover relative to that of tyramine (kcat approximately 50 s(-1), despite the nearly 100-fold higher affinity of the inactivator for enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Characterization of selected Spanish table wine samples according to their biogenic amine content from liquid chromatographic determination.

Pattern recognition techniques, such as principal component analysis, cluster analysis, and linear discriminant analysis, have been applied to samples of red, white, and rosé wines to determine whether some biogenic amines could be considered as chemical descriptors. Eight amines (tryptamine, phenylethylamine, putrescine, cadaverine, histamine, tyramine, spermidine, and spermine) were determined by RP-HPLC, after derivatization with dabsyl chloride. However, only putrescine, cadaverine, histamine, tyramine, spermidine, and spermine were found in the wines analyzed. From the association between variables obtained by principal component analysis and clustering and from the relationship found by linear discriminant analysis, it can be deduced that the amines generated during malolactic fermentation (putrescine, histamine, and tyramine) could be used as chemical descriptors to characterize table wine samples.

Analysis of Variance↗

Purification and immunochemical characterization of monoamine oxidase from rat and human liver.

1. Monoamine oxidase from rat and human liver was purified to homogeneity by the criterion of polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. 2. The enzyme activity was extracted from mitochondrial preparations by Triton X-100. The enzyme was purified by (NH4)2SO4 fractionation followed by chromatography on DEAE-cellulose, Sepharose 6B, spheroidal hydroxyapatite, and finally chromatography on diazo-coupled tyramine-Sepharose. 3. Distinct differences occur in the chromatographic behaviour of the two enzymes on both DEAE-cellulose and spheroidal hydroxyapatite. 4. It is unlikely that the purification of the enzymes on tyramine-Sepharose is due to affinity chromatography and reasons for this are discussed. 5. The purified enzymes did not oxidize-5-hydroxytryptamine and the relative activities of the enzymes with benzylamine were increased approx. 1.25-fold compared with the enzyme activities of mitochondrial preparations. 6. Immunotitration of enzyme activity in extracts of mitochondrial preparations from rat liver was carried out with 5-hydroxytryptamine, tyramine and benzylamine. The enzyme activities were completely immunoprecipitated by the same volume of antiserum. Similar results were obtained with the antiserum to the enzyme from human liver.

Animals↗

Reduction of membrane-bound dopamine beta-hydroxylase from the cytoplasmic surface of the chromaffin-granule membrane.

Resealed bovine chromaffin-granule 'ghosts' were used for assaying the membrane-bound form of dopamine beta-hydroxylase. Hydroxylation of the substrate tyramine is dependent on its accumulation within the 'ghosts', where the active site of the enzyme is located. Free tyramine in the medium is at a low concentration, low ionic strength and a relatively high pH (7.0), so that even in the presence of a reducing agent (co-reductant) the unaccumulated amine is hydroxylated at a negligible rate. 'Ghosts' contain an endogenous co-reductant, which is shown to be catecholamine remaining in the membrane itself after granule lysis. Catecholamine that is free in solution in the medium or in the interior of the 'ghosts' is not effective as co-reductant, nor is ascorbate, in contrast with the situation with soluble dopamine beta-hydroxylase. Ferrocyanide is an active co-reductant, however, giving a hydroxylation rate approximately equal to the tyramine accumulation rate: it does not enter the 'ghosts', nor does the enzyme appear to utilize ferrocyanide sealed inside the 'ghosts'. A mechanism must therefore exist for transferring electrons across the membrane from the cytoplasmic surface to the matrix surface. NADH is not an electron donor for the enzyme, nor is cytochrome b-561 involved.

Animals↗

Noradrenaline release in skeletal muscle and in adipose tissue studied by microdialysis.

1. In adipose tissue and in skeletal muscle the extracellular noradrenaline levels were studied by microdialysis in the conscious dog and compared with the noradrenaline concentration in arterial plasma. 2. The experiments were performed with and without tyramine added to the perfusion medium, and noradrenaline was measured by a sensitive radioenzymic assay. 3. In the absence of tyramine, the interstitial noradrenaline levels in adipose tissue and skeletal muscles were similar to arterial blood concentrations, provided that the former were corrected for recovery. The recovery estimated from experiments in vitro averaged 16% at room temperature. 4. With tyramine added to the perfusates, noradrenaline levels increased 10-fold. Arterial noradrenaline concentrations did not change, indicating that noradrenaline was released only locally in the tissue. 5. Our results indicate that the microdialysis technique combined with a sensitive assay for measuring noradrenaline may be applicable to the assessment of local noradrenaline release in adipose tissue and in skeletal muscle. This may be of interest, especially in adipose tissue during physiological stimulation in which sympathetic activity is difficult to evaluate by other techniques.

Adipose Tissue↗

Prior exposure to lipopolysaccharide potentiates expression of plant defenses in response to bacteria.

Lipopolysaccharide (LPS) is a ubiquitous component of Gram-negative bacteria which has a number of diverse biological effects on eukaryotic cells. In contrast to the large body of work in mammalian and insect cells, the effects of LPS on plant cells have received little attention. LPS can induce defense-related responses in plants, but in many cases these direct effects are weak. Here we have examined the effects of prior inoculation of LPS on the induction of plant defense-related responses by phytopathogenic xanthomonads in leaves of pepper (Capsicum annuum). The resistance of pepper to incompatible strains of Xanthomonas axonopodis pv. vesicatoria or to X. campestris pv. campestris is associated with increased synthesis of the hydroxycinnamoyl-tyramine conjugates, feruloyl-tyramine (FT) and coumaroyl-tyramine (CT). FT and CT are produced only in trace amounts in response to compatible strains of X. axonopodis pv. vesicatoria. Treatment of leaves with LPS from a number of bacteria did not induce the synthesis of FT and CT but altered the kinetics of induction upon subsequent bacterial inoculation. In incompatible interactions FT and CT synthesis was accelerated, whereas in compatible interactions synthesis was also considerably enhanced. The ability of the tissue to respond more rapidly was induced within 4 h of LPS treatment and the potentiated state was maintained for at least 38 h. Earlier treatment with LPS also potentiated the expression of other defense responses such as transcription of genes encoding acidic beta-1,3-glucanase. Our findings indicate a wider role for LPS in plant-bacterial interactions beyond its limited activity as a direct inducer of plant defenses.

Capsicum↗

Why do some dietary migraine patients claim they get headaches from placebos?

BACKGROUND: In six double-blind studies involving 182 tests of dietary migraine patients sensitive to tyramine and beta-phenylethylamine, 18% reported headaches from placebos which were all concealed in gelatin capsules. OBJECTIVE: The purpose of this research was to test a hypothesis: gelatin is partially hydrolysed animal protein; (partially) hydrolysed vegetable protein (PHVP) is known to cause migraine; perhaps the gelatin caused some of the headaches. METHOD: The author tested this hypothesis on himself because he suffers from dietary migraine. He proved this in a double-blind test with tyramine hydrochloride (TYH). The amount required for the test was so small (1 mg) that it was tasteless and capsules were unnecessary. The author then undertook tests with a capsule, PHVP, monosodium glutamate (MSG) aspartame (a dipeptide) and TYH, adjusting quantities to give a moderate headache. Samples were mixed with foods to simulate normal eating: the capsule with potato chips, aspartame with orange juice and the rest with cottage cheese or ricotta cheese. Times were measured from ingestion (1) to start of the headache and (2) to maximum headache intensity. Each experiment was repeated three times. The headaches were relieved with caffeine. RESULTS: Of eight double-blind test samples, the author identified correctly the two placebos and five of the six samples containing tyramine. Quantities giving moderate headaches were: 1 gelatin capsule, 400 mg MSG, 118 mg PHVP, 4.0 mg aspartame and 1.0 mg TYH. Typical times for the three repetitions of the two time periods were 8, 9 and 11 and 17, 19 and 22 min. CONCLUSIONS: Capsules may give headaches to dietary migraine patients that are similar to those from foods. This would explain some of the headaches of patients from placebos. The double-blind test and the repeatability of the time measurements demonstrated the validity of the experiments.

Analgesics↗

Latent dysautonomic pupillary lateralization in cluster headache. A pupillometric study.

Forty-five patients with cluster headache in the asymptomatic phase were studied by electronic pupillography, testing autonomic function of both pupils pharmacologically. Topical sympathetically-acting mydriatics, tyramine and cocaine and the cholinoceptor blocker, homatropine, induced defective mydriatic responses on the symptomatic side, indicating latent impairment of sympathetic function. The abnormality was found in interattack intervals of the cluster period or during intercluster phases. The tyramine test can be proposed for objective diagnosis of cluster headache. We postulate that cluster attacks are triggered and lateralized by a permanent latent unilateral sympathetic dysfunction. Lithium reduced the mydriatic response to tyramine of the pupil contralateral to the pain, thus restoring the equilibrium between both pupils; this therapy may correct the asymmetric sympathetic function by attenuating the activity in the asymptomatic side.

Adolescent↗

Coexistence of pupillary and heart sympathergic asymmetries in cluster headache.

Ten cluster headache patients and 10 healthy controls were subjected to electrocardiographic and pupillometric procedures in a search for cardiac and pupillary sympathergic asymmetry. Sympathergic stimulation was provoked by hyperventilation and by instilling tyramine into both eyes. In the control group, hyperventilation changed neither the T-wave form and polarity nor the QTc. Tyramine provoked an equal mydriasis on the two sides. In cluster headache sufferers, hyperventilation produced changes in the T-wave form and polarity as well as an increase of the QTc due to a disproportionate shortening of the R-R and Q-T intervals. An unequal mydriasis was noted after tyramine instillation due to less marked response on the symptomatic side. The observed electrocardiographic abnormalities are considered an expression of an asynchronous repolarization attributed to a sympathergic asymmetry. It is postulated that both the cardiac and pupillary sympathetic imbalance associated with cluster headache are central in origin.

Adolescent↗