Simultaneous electrochemical measurement method of histamine and N(τ)-methylhistamine by high-performance liquid chromatography-amperometry with o-phthalaldehyde-sodium sulfite derivatization.

An electrochemical detection (ECD) method for analyzing sub-micro amounts of histamine (HA) and N(τ)-methylhistamine (N(τ)-MHA) in biological samples by high-performance liquid chromatography (HPLC)-amperometry has been developed. The method consists of a precolumn derivatization of the amines with o-phthalaldehyde (OPA) and sodium sulfite (Na(2)SO(3)) to N-alkyl-1-isoindole sulfonate and posterior separation with the HPLC system. Biological samples were pretreated by using a Vivapure sulfonic acid minifilter in which the reaction of the reagent with the amines took place during filtering. HA and N(τ)-MHA retention times were 11.8 ± 0.02 and 18.3 ± 0.03 min, respectively (means ± standard deviations, n = 3). The lowest limit of amperometric detection at a signal-to-noise ratio of 3:1 was 0.125 pmol in both cases. HA and N(τ)-MHA contents in hypothalamus, cortex, skin, and fundic gland, as well as histamine N-methyltransferase (HMT) activities of mast cell-deficient (Ws/Ws) and Wistar rats, were measured and compared with an HPLC-fluorometry system, among other experiments, in order to validate and demonstrate the usefulness of this assay system. Hence, this consequently confirms not only the sensitivity and specificity of the assay but also the potential and convenience it offers to laboratory work, especially in the analysis of the regulation of histaminergic neurons as well as enzymatic investigation of HA metabolism.

Simultaneous quantitation of histamine and its major metabolite 1-methylhistamine in brain dialysates by using precolumn derivatization prior to HILIC-MS/MS analysis.

In nonclinical drug development targeting the central nervous system (CNS), the quantitative determination of extracellular brain concentrations of neurotransmitters is a key challenge. In some CNS disorders, the monitoring of the modified profile of neurotransmitter release such as that of histamine may explain the mechanism of action of the drug candidate. Microdialysis is a commonly used method for sampling extracellular levels of neurotransmitters/drug candidates in small laboratory animals. Detection and quantification of extracellular levels of neurotransmitters remain an analytical and technical challenge owing to the low concentrations of neurotransmitters collected, the small microdialysis sample size, and the high amount of inorganic salts. A precolumn derivatization strategy prior to hydrophilic interaction liquid chromatography (HILIC)-tandem mass spectrometry analysis is proposed to quantify histamine release after administration of a CNS research compound. Derivatization using propionic anhydride dissolved in organic solvent combined with the HILIC approach effectively eliminated three time-consuming steps, organic layer transfer, dry down, and reconstitution, all of which are required by traditional reversed-phase liquid chromatography. The formation of propionylated amides, performed under mild conditions, required no further sample cleanup. After a dual microdialysis probe implantation into the prefrontal cortex (neurotransmitters) and in the inferior vena cava of rat (drug candidate), microdialysate fractions were collected every 15 min for 8 h and stored frozen at -20 °C until analysis. The method was validated using 10 µL microdialysate, achieving low limits of quantitation of 83.4 and 84.5 pg.mL(-1) for histamine and 1-methylhistamine, respectively. These limits were suitable to assess kinetic release of neurotransmitters and are compatible with those obtained by microdialysis sampling. This method provided the required selectivity, sensitivity, accuracy, and precision to assess release kinetics of histamine and 1-methylhistamine in several hundred rat brain microdialysates after intravenous infusion of CNS drug candidates.

Activation of brain histaminergic neurotransmission: a mechanism for cognitive effects of memantine in Alzheimer's disease.

We previously reported that some N-methyl-D-aspartate (NMDA)-receptor antagonists enhanced histamine neuron activity in rodents. Here, we have investigated the effects of memantine, an NMDA-receptor antagonist used for the treatment of Alzheimer's disease, on histaminergic neurotransmission. In vitro, memantine antagonized native NMDA receptors with a micromolar potency but had no effect at recombinant human histamine receptors. In vivo, a single administration of memantine increased histamine neuron activity, as shown by the 60% increase of tele-methylhistamine (t-MeHA) levels observed in the brain of mice. This increase occurred with an ED(50) of 0.3 ± 0.1 mg/kg, similar to that found on inhibition of ex vivo [(3)H]dizocilpine maleate (MK-801) binding (1.8 ± 1.3 mg/kg). Two days after pretreatment of mice with memantine at 5 mg/kg twice daily for 5 days, t-MeHA levels were enhanced by 50 ± 7% (p < 0.001), indicating a long-lasting activation of histamine neurons. Quantitative polymerase chain reaction analysis was used to explore genes involved in this persistent effect. H(3) receptor mRNAs were strongly increased, but the density of H(3) receptor binding sites was increased solely in hypothalamus (by 141 ± 24%). Up-regulations of brain-derived neurotrophic factor and NMDA-receptor 1 subunit mRNAs were also found but were restricted to hippocampus. mRNA expression of α7-nicotinic receptors remained unchanged in any region. Considering the well established cognitive effects of histamine neurons, the increase in brain t-MeHA levels after single or repeated administration of therapeutic doses of memantine suggests that the drug exerts its beneficial effects on cognitive deficits of Alzheimer's disease, at least partly, by activating histamine neurons.

Systematic analysis of histamine and N-methylhistamine concentrations in organs from two common laboratory mouse strains: C57Bl/6 and Balb/c.

OBJECTIVE: Histamine plays a role in several (patho) physiological processes that are commonly studied in mouse models. However, a systematic quantification of histamine and its metabolite N-methylhistamine in mouse organs has not been reported so far. METHODS: Balb/c and C57Bl/6 mice were grouped according to their sex and age. Brains, hearts, lungs, livers, kidneys, stomachs, intestines, thymi, spleens, and lymph nodes were excised, weighed, and homogenized. Histamine and N-methylhistamine were quantified simultaneously by a HPLC-mass spectrometry method. RESULTS: In all organs analyzed, histamine and N-methylhistamine were detected; however, with quantitative differences. Histamine was present most abundantly in the stomach, lymph nodes, and thymus. The lowest histamine concentrations were detected in brain, liver, lung, and intestine. In most organs, the histamine concentrations increased age-dependently. Substantial concentrations of N-methylhistamine were detected only in lung, intestine and kidney, while in all other organs it was present only in minor quantities. CONCLUSION: HPLC-mass spectrometry is a useful method for the highly sensitive and simultaneous detection of histamine and N-methylhistamine. Histamine is present in virtually all organs, not only in those traditionally associated with histamine-mediated disease. Highest concentrations are found in stomach, lymph node, and thymus; medium concentrations in heart, spleen, and kidney; and lowest concentrations detected in intestine, brain, liver, and lung.

Gas chromatography-mass spectrometry assay for determination of Ntau-methylhistamine concentration in canine urine specimens and fecal extracts.

OBJECTIVE: To develop and validate a gas chromatography-mass spectrometry (GC-MS) method for determination of Ntau-methylhistamine (NMH) concentration in canine urine and fecal extracts and to assess urinary NMH concentrations in dogs with mast cell neoplasia and fecal NMH concentrations in dogs with protein-losing enteropathy. SAMPLE POPULATION: Urine specimens were collected from 6 healthy dogs and 7 dogs with mast cell neoplasia. Fecal extracts were obtained from fecal specimens of 28 dogs with various severities of protein-losing enteropathy, as indicated by fecal concentration of alpha1-proteinase inhibitor. PROCEDURES: NMH was extracted directly from urine, and fecal specimens were first extracted into 5 volumes of PBSS containing 1% newborn calf serum. Ntau-methylhistamine in specimens was quantified via stable isotope dilution GC-MS. The assay was validated via determination of percentage recovery of known amounts of NMH and interassay coefficients of variation. Urinary excretion of NMH was evaluated by means of NMH-to-creatinine concentration ratios. RESULTS: Recovery of NMH in urine and fecal extracts averaged 104.6% and 104.5%, respectively. Interassay coefficients of variation ranged from 5.4% to 11.7% in urine and 12.6% to 18.1% in fecal extracts. Urinary NMH excretion was significantly increased in dogs with mast cell neoplasia, compared with that in healthy dogs. No correlation was detected between severity of protein-losing enteropathy and fecal NMH concentration. CONCLUSIONS AND CLINICAL RELEVANCE: This method provided a sensitive, reproducible means of measuring NMH in canine urine and fecal extracts. High urinary NMH-to-creatinine concentration ratios in dogs with mast cell neoplasia are consistent with increased histamine release in this disease.

Hair analysis of histamine and several metabolites in C3H/HeNCrj mice by ultra performance liquid chromatography with electrospray ionization time-of-flight mass spectrometry (UPLC-ESI-TOF-MS): influence of hair cycle and age.

BACKGROUND: According to a previous study, the concentration of HA in the hair of SD rats was similar in each rat and the variation in HA concentration was not so great. However, the concentration in human hair was fairly different in each person. As possible reasons for the higher variation in human hair, the differences in hair cycles and age in each person may be considerable. Based on this idea, the studies using C3H/HeNCrj mice who can synchronize their hair cycle were performed for resolution of the influence of hair cycle and age. METHODS: The effects of hair cycle and age on the concentration of histamine (HA) and several metabolites, i.e., 1-methylhistamine (MHA), imidazole-4-acetic acid (IAA), and 1-methyl-4-imidazole-acetic acid (MIAA), in C3H/HeNCrj mice hair were investigated by ultra-performance liquid chromatography (UPLC) with electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS). HA and the metabolites were labeled with 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD-F) and 4-(N,N-dimethylaminosulfonyl)-7-piperazino-2,1,3-benzoxadiazole (DBD-PZ). The resulting derivatives were separated by UPLC and determined with ESI-TOF-MS. RESULTS: A good linearity was achieved from the calibration curves, obtained by plotting the peak area ratios of the analytes relative to the internal standard (IS), i.e., histamine-alpha,alpha,beta,beta-d4 (HA-d4) or 4-imidazolecarboxylic acid (ICA), against the injected amounts of each compound. The detection limits of HA, MHA, IAA, and MIAA on mass chromatograms were 0.21, 1.0, 0.17, and 0.11 pmol, respectively. The concentrations of HA and the metabolites in the hair shafts and hair root of C3H/HeNCrj mice were determined by this method. The concentration of HA in the hair shaft was relatively higher in the telogen phase. In contrast, the HA content in the anagen phase was increased only in the hair root of old mice. CONCLUSION: HA appears to possess some effect on hair growth, although the exact reason was not obvious. The HA metabolites, i.e., MHA, MIAA and IAA, were also determined the same as HA; however, the difference in the metabolite concentrations between the hair cycle and age was not clear in both hair shaft and hair root. Such studies of the effect of hair cycle and age on these concentrations are the first report. This analytical technique may be applicable to the determination of various biological compounds in hair.

A liquid chromatographic method for the determination of histamine in immunoglobulin preparation using solid phase extraction and pre-column derivatization.

An immunoglobulin (IgG) preparation with micro-amount of histamine fixed on the active protein fraction has been used to increase the resistance to allergic reactions. However, excessive histamine may cause hypo- or hypertension, headache, or anaphylactic shock and so the histamine content of the drug is strictly controlled by a regulation: 0.15 microg of histamine dihydrochloride is allowed for 12 mg of immunoglobulin. In this study, a liquid chromatographic method to determine micro-amount of histamine in the pharmaceutical was developed and validated. This method include a sample cleanup by a solid phase extraction (SPE) using a polystyrene-divinyl benzene (PS-DVB) polymeric sorbent and high-performance liquid chromatography after precolumn fluorescent labeling of the histamine with o-phthaldialdehyde. The drug sample was loaded to the SPE cartridge after adjusting to pH 9.5. After successive washings of the cartridge with water and 30% aqueous methanol, histamine was then eluted with 100 mM sodium acetate (pH 9.5)-methanol (20:80, v/v). An aliquot from the eluate was labeled with o-phthaldialdehyde-mercaptoethanol (OPA-ME) for fluorescence detection at the excitation maximum of 340 nm and emission maximum of 450 nm. HPLC analysis was performed on a phenyl-hexyl column with an acetonitrile-phosphate buffer (pH 6.8; 50 microM) (35:65, v/v) as the mobile phase. The retention times of histamine and 3-methylhistamine (IS) were approximately 7.2 and 9.5 min, respectively. The quantitation range was between 0.01-0.2 mg/mL of histamine showing good linearity (r=0.9996). This analytical method would provide a potential mean for the strict control of histamine content in the pharmaceutical product.

Glucagon-like peptide-1, corticotropin-releasing hormone, and hypothalamic neuronal histamine interact in the leptin-signaling pathway to regulate feeding behavior.

Glucagon-like peptide-1 (GLP-1), corticotropin-releasing hormone (CRH), and hypothalamic neuronal histamine suppress food intake, a target of leptin action in the brain. This study examined the interactions of GLP-1, CRH, and histamine downstream from the leptin-signaling pathway in regulating feeding behavior. Infusion of GLP-1 into the third cerebral ventricle (i3vt) at a dose of 1 mug significantly decreased the initial 1 h cumulative food intake in rats as compared with phosphate-buffered saline (PBS) controls. The GLP-1-induced suppression of feeding was partially attenuated by intraperitoneal pretreatment with alpha-fluoromethylhistidine (FMH), a specific suicide inhibitor of histidine decarboxylase, which depletes hypothalamic neuronal histamine. Pretreatment with alpha-helical CRH (10 microg/rat, i3vt), a nonselective CRH antagonist, abolished the GLP-1-induced suppression of feeding completely. I3vt infusion of GLP-1 increased the CRH content and histamine turnover assessed using the pargyline-induced accumulation of tele-methyl histamine (t-MH), a major metabolite of neuronal histamine, in the hypothalamus. The central infusion of CRH also induced the increase of histamine turnover and CRH receptor type 1 was localized on the cell body of histamine neuron. Pretreatment with exendin(9-39), a GLP-1 receptor antagonist, attenuated the leptin-induced increase in CRH content of the hypothalamus. Finally, i3vt infusion of leptin also increased histamine turnover in the hypothalamus. Pretreatment with exendin(9-39), alpha-helical CRH or both antagonists attenuated the leptin-induced responses of t-MH levels in the hypothalamus. These results suggest that CRH or hypothalamic neuronal histamine mediates the GLP-1-induced suppression of feeding behavior, that CRH mediates GLP-1 signaling to neuronal histamine and that a functional link from GLP-1 to neuronal histamine via CRH constitutes the leptin-signaling pathway regulating feeding behavior.

High-performance liquid chromatographic method for the determination of histamine and 1-methylhistamine in biological buffers.

A method for the determination of histamine and its catabolite 1-methylhistamine (1-MH) was developed, using HPLC with fluorescence detection. Derivatization of both compounds occurred on-column with o-phthaldialdehyde dissolved in an alkaline borate buffer, followed by separation on a reversed phase C18 column. Histamine and 1-MH could be detected with comparable sensitivity (limit of quantification, 50 nM). The method was proven suitable to investigate catabolism of histamine by epithelia of pig colon. The method should be useful in research on histamine metabolism.

Mastocytosis and adverse reactions to biogenic amines and histamine-releasing foods: what is the evidence?

BACKGROUND: It has been suggested that normal concentrations of biogenic amines and 'histamine-releasing foods' may exacerbate symptoms in mastocytosis. The purpose of this study was to look for scientific evidence in the literature on diets restricted in biogenic amines and histamine-releasing foods in the treatment of mastocytosis. METHODS: Medline (1966 to 2004), Cinahl (1982 to 2004) and the Cochraine Library were searched for double-blind placebo-controlled food challenge (DBPCFC) studies with biogenic amines and/or histamine-releasing foods in mastocytosis. RESULTS: No studies employing DBPCFC with dietary biogenic amines or histamine-releasing foods in mastocytosis were found. Only a few in vitro studies in other diseases, animal studies and studies in humans in which histamine-releasing agents were incubated directly with duodenal tissues were found. One case was reported of severe adverse reactions to alcohol in mastocytosis, objectified by an open challenge. CONCLUSION: Despite the widespread belief that biogenic amines and histamine-releasing foods may cause allergy-like, non-IgE-mediated symptoms in certain patients, the role of diets restricted in biogenic amines and histamine-releasing foods in the treatment of mastosytosis remains hypothetical but worthy of further investigation. There is some evidence for adverse reactions to alcohol in mastocytosis.

An immunoassay for histamine based on monoclonal antibodies.

Monoclonal antibodies with high specificity for histamine as well as for 1-methylhistamine were obtained after immunization of mice with a conjugate where the histamine was coupled via its ring 1-nitrogen to dog serum albumin. An immunoassay was developed for the quantitation of histamine release from basophils and 1-methylhistamine release from mast cells after provocation. The test method is based on competitive inhibition between histamine and a labelled histamine conjugate for the antigen binding sites of the antibodies. The separation step is performed by the addition of solid phase bound anti-mouse subclass specific antibodies. The sensitivity of the assay is 2 micrograms/l for histamine and 0.1 micrograms/l for 1-methylhistamine. No cross-reactivity was obtained with other metabolites of histamine or with histidine. Serotonin and dopamine were detectable, but only in doses (mg/l) well above the normal concentration found in the circulation. The immunoassay has been evaluated for its capacity to measure histamine release in vitro. A good correlation with the conventional fluorometric assay was obtained when histamine released from allergen stimulated leucocytes from allergic patients was tested. Urinary samples from patients undergoing hyposensitization showed a mean excretion of 1-methylhistamine at a level of 131 mumol MeHi/mol creatinine. The release of histamine and 1-methylhistamine in vivo was examined in plasma samples taken during a bronchial provocation test. A significant elevation above the basal analyte level occurred ten minutes after provocation.

Regional distribution of histamine and tele-methylhistamine in the rat, mouse and guinea-pig brain.

Regional histamine (HA) and tele-methylhistamine (t-MH) contents were determined in the rat, mouse and guinea-pig brain. The highest HA and t-MH levels were found in the hypothalamus of all species. Fairly high t-MH levels were observed in the amygdala of all species and in the guinea-pig hippocampus. The t-MH/HA ratio was higher in the regions of the telencephalon than in the diencephalon and brainstem. The cerebellum and spinal cord showed extremely low t-MH/HA ratios. These results suggest higher histaminergic neuronal activities in the hypothalamus and some regions of the telencephalon than in other parts of the brain.

Decrease in histamine turnover in the brain of spontaneously hypertensive rats.

Histamine (HA) turnover rate in the brain of spontaneously hypertensive rats (SHR) was determined by the accumulation of telemethylhistamine after pargyline treatment. The values in these SHR were lower than in the Wistar Kyoto rats, particularly in the hypothalamus and brainstem. However, chronic treatment with L-histidine had no effect on the development of hypertension in the SHR. The functional significance of the decreased HA turnover in SHR is discussed in relation to the pathogenesis of hypertension.

Normal levels of histamine and tele-methylhistamine in mast cell-deficient mouse brain.

To determine the contribution by mast cells to the brain content of histamine (HA) and its metabolite tele-methylhistamine (t-MH), the number of mast cells, as well as the levels of HA and t-MH were measured in brain regions of mast cell-deficient (W/Wv) and control (+/+) mice. In agreement with earlier studies, mast cells were identified in control mouse brains, whereas W/Wv brains were devoid of mast cells. Contrary to earlier studies, no differences between these strains were found in the HA levels of any brain region, implying that mouse brain mast cells do not contribute significantly to brain HA levels. Brain t-MH levels were also not different between strains, except in hypothalamus, where W/Wv levels were higher; a significantly smaller W/Wv hypothalamus accounted for this difference. It is not certain that such differences are due to the absence of mast cells, since the W/Wv mutant is pleiomorphic, and the biochemical nature of this mutation remains uncertain. However, the absence of mast cells and presence of HA in the W/Wv mouse brain is direct evidence for the existence of non-mast cell HA in the brain. These results also show that mouse brain t-MH levels are predictive of non-mast cell HA in brain.

Hypothalamic neuronal histamine in genetically obese animals: its implication of leptin action in the brain.

Leptin regulates feeding behavior and energy metabolism by affecting hypothalamic neuromodulators. The present study was designed to examine hypothalamic neuronal histamine, a recently identified mediator of leptin signaling in the brain, in genetic obese animals. Concentrations of hypothalamic histamine and tele-methylhistamine (t-MH), a major histamine metabolite, were significantly lower in obese (ob/ob) and diabetic (db/db) mice, and Zucker fatty (fa/fa) rats, leptin-deficient and leptin-receptor defective animals, respectively, relative to lean littermates (P < 0.05 for each). A bolus infusion of leptin (1.0 microg) into the lateral ventricle (ilvt) significantly elevated the turnover rate of hypothalamic neuronal histamine, as assessed by pargyline-induced accumulation of t-MH, in ob/ob mice compared with phosphate-buffered saline (PBS) infusions (P < 0.05). However, this same treatment did not affect hypothalamic histamine turnover in db/db mice. In agouti yellow (A(y)/a) mice, animals defective in pro-opiomelanocortin (POMC) signaling, normal levels of histamine, and t-MH were seen in the hypothalamus at 4 weeks of age when obesity had not yet developed. These amine levels in A(y)/a mice showed no change until 16 weeks of age, although the mice were remarkably obese by this time. Infusions of corticotropin releasing hormone (CRH), one of neuropeptide related to leptin signaling, into the third ventricle (i3vt) increased histamine turnover in the hypothalamus of Wistar King A rats (P < 0.05 versus PBS infusion). Infusion of neuropeptide Y (NPY) or alpha-melanocyte stimulating hormone (MSH), a POMC-derived peptide failed to increase histamine turnover. These results indicate that lowered activity of hypothalamic neuronal histamine in ob/ob and db/db mice, and fa/fa rats may be due to insufficiency of leptin action in the brains of these animals. These results also suggest that disruption of POMC signaling in A(y)/a mice may not impact on neuronal histamine. Moreover, CRH but neither POMC-derived peptide nor NPY may act as a signal to neuronal histamine downstream of the leptin signaling pathway.

The effect of REM sleep deprivation on histamine concentrations in different brain areas.

Rats were deprived of REM sleep (REMS) for 72 h with the platform method and decapitated in the morning immediately after the deprivation or in the afternoon after having been allowed 5 hours of rebound sleep. The histamine concentrations of the anterior and posterior hypothalamus, the cortex, the hippocampus and the pineal gland were measured, as well as the tele-methylhistamine concentrations of the anterior and posterior hypothalamus. Histamine concentrations were no different after REMS deprivation compared to large platform or dry cage controls, but in the anterior hypothalamus histamine levels increased during rebound sleep only in the REMS deprived rats. tele-Methylhistamine/histamine ratios were higher after 72 h of both REMS deprivation and the large platform treatment compared to dry cage controls, indicating increased histamine utilization during the platform treatment procedure.

A simple and sensitive determination of histamine and N tau-methylhistamine in biological fluids by high-performance liquid chromatography with electrochemical detection.

The determination of picomolar levels of histamine and its major metabolite, N tau-methylhistamine, in biological fluids was achieved using reversed-phase liquid chromatography coupled with electrochemical detection. A simple sample purification procedure for blood and urine samples was carried out prior to analysis using an Amberlite CG-50 cation-exchange resin, which afforded an excellent recovery of both compounds.

Cerebral and gastric histamine system is altered after portocaval shunt.

Biochemical parameters of the histamine (HA) system were examined in both rat brain and stomach, after portocaval anastomosis (PCA). These tissues become rich in histamine after PCA. Immunocytochemistry was used for brain histamine localisation. In addition to increased HA concentrations, monoamine oxidase B activity increased in both tissues. In hypothalamus HA was 15 fold; in cerebral cortex and in stomach mucosa 2.8 and 2.5 fold of the corresponding controls, respectively. MAO B activity was increased by approximately 50% in brain and 100% in stomach. A significant, uneven increase in tele-methylhistamine concentration was only found in the brain. In stomach mucosa higher histidine decarboxylase activity was found. PCA and sham rats treated with an irreversible inhibitor of MAO B, FA-73, 0.5 mg/kg i.p., showed 24 h later greatly reduced MAO activity and doubled t-MeHA concentration in brain structures. The treatment had no effect on gastric mucosal t-MeHA concentration and urinary excretion of the t-MeHA metabolite, N-tele-methylimidazoleacetic acid. The HA rise in the stomach of PCA rats is associated with proliferation of histamine producing and storing cells (ECL cells) as demonstrated by others. However, in the brain we saw no indication for increased number of relevant cells either mast cells or neurons and our immunocytochemical findings suggest that in PCA rat brain, histamine deposits are located exclusively in neurons. The data indicate that the adaptative mechanisms to excessive histamine formation are tissue specific.

Cactus alkaloids. XLVII. N alpha-dimethylhistamine, a hypotensive component of Echinocereus triglochidiatus.

Echinocereus triglochidiatus Engelm. var. neomexicanus (Standley) Standley ex W. T. Marshall is believed to cause psychotropic effects when consumed by the Mexican Tarahumara Indians. A phytochemical study was initiated with E. triglochidiatus Engelm. var. paucispinus Engelm. ex W. T. Marshall, which is more abundant in Texas. In the fractionated extracts three compounds, detected by thin-layer chromatography, were positive to Ehrlich's reagent, indicating the possible presence of indole alkaloids; however, a non-Erhlich positive alkaloid was crystallized as the dihydrochloride and subsequently identified (spectrometrically and via synthesis as N alpha, N alpha-dimethylhistamine dihydrochloride. The same compound was then detected chromatographically in the neomexicanus variety. This compound has peripheral hypotensive effects similar to histamine, and this action may help to explain the alleged psychotrophic effects of the cactus.

Role of histamine in motion sickness in Suncus murinus.

The levels of histamine (HA) and tele-methylhistamine (t-MH) were determined in five brain regions of Suncus murinus (suncus) and the effects of motion stimulus or drugs influencing the turnover of these amines were studied to elucidate the role of histamine in motion sickness. Shaking the animals for 2 min increased HA contents in telencephalon and diencephalon without significantly changing the t-MH levels. alpha-Fluoromethylhistidine (alpha-FMH), which is presumed to deplete the neuronal HA, tended to raise the HA levels. alpha-FMH slightly alleviated the vomiting response to motion stimulus and suppressed the HA increase in diencephalon caused by shaking. Compound 48/80, which releases HA from mast cells, did not alter the control HA levels, but effectively prevented the motion sickness and completely suppressed the motion-induced rises in HA levels. These results provide further evidence that brain HA plays an important role in the development of motion sickness.