Spermine tetrahydrochloride

Biogenic amines profile and concentration in commercial milks for infants and young children.[Pubmed:30722764]

Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2019 Mar;36(3):337-349.

Commercial milks for infants and young children (CMIYC) received much attention during last years for their impact on the nutritional status, health and development of the new-born and babies. Among possible contaminants contained in these foods, biogenic amines (BAs) have rarely been determined although they can exert toxic effects in humans if ingested at high concentrations. Spermine, spermidine, putrescine, histamine, tyramine, beta-phenylethylamine and cadaverine have been quantified in CMIYC samples by LC-UV after derivatisation with dansyl-chloride. Once optimised in terms of linearity (R(2) >/= 0.989), recovery percentages (92.9-97.3), LOD (0.2-0.4 mug g(-1) or 0.03-0.05 mug mL(-1) depending on the samples), LOQ (0.5-1.0 mug g(-1) and 0.08-0.13 mug mL(-1) depending on the samples) and repeatability (0.1-0.2 intra-day; 0.2-0.4 inter-day), the method has been applied to real samples. Very low total BAs concentrations have been found in reconstituted (1.18-3.12 mg L(-1)) and liquid milks (0.33-2.30 mg L(-1)), with different biogenic amine profiles and distributions. A risk assessment based on the available information regarding Acute Reference Doses of histamine and tyramine, as well as the application of common Biogenic Amine Indexes, showed that none of the analysed samples represented a possible risk for babies, also considering a worst case evaluation. These findings confirmed the strict safety and quality protocols adopted during the production of CMIYC. Chemical compounds studied in this article: Ammonium chloride (PubChem CID: 25517); Cadaverine hydrochloride (PubChem CID: 5351467); Hydrochloridric acid (PubChem CID: 313); Histamine dihydrochloride (PubChem CID: 5818); Phenylethylamine hydrochloride (PubChem CID: 9075); Putrescine dihydrochloride (PubChem CID: 9532); Sodium hydroxide (PubChem CID: 14798); Spermine tetrahydrochloride (PubChem CID: 1103); Spermidine trihydrochloride (PubChem CID: 1102); Tyramine hydrochloride (PubChem CID: 66449).

Polyamine co-matrices for matrix-assisted laser desorption/ionization mass spectrometry of oligonucleotides.[Pubmed:10510414]

Rapid Commun Mass Spectrom. 1999;13(20):2014-21.

The analysis of oligonucleotides using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has led to the investigation of the use of matrix additives (i.e., co-matrices) to help improve the poor spectral quality commonly observed during the analysis of this class of compounds. The use of certain matrix additives in MALDI-MS has been investigated previously, and these additives have been shown to enhance the desorption/ionization efficiency of oligonucleotides during the MALDI experiment. Specifically, amine bases, such as piperidine, imidazole, and triethylamine, have been shown to improve mass spectral quality as assessed by improved molecular ion resolution and increased molecular ion abundance. These improvements occur due to competition between the oligonucleotide and the co-matrix for protons generated during the MALDI event. Co-matrices with proton affinities near or above the proton affinities of the nucleotide residues serve as proton sinks during the desorption/ionization process. In this work, we have investigated the use of polyamines as co-matrices for MALDI mass spectrometric analysis of oligonucleotides. Spermine tetrahydrochloride, spermine, spermidine trihydrochloride, and spermidine were evaluated for their effectiveness at enhancing the mass spectral quality of oligonucleotides analyzed using MALDI-MS. The solution-phase pK( b) values and the gas-phase proton affinities of these polyamines were determined, and it was found that the polyamines appear to be more basic than the monofunctional amines investigated previously. The mass spectral data shows that spermidine and spermine are extremely effective co-matrices, yielding improved molecular ion resolution and molecular ion abundances. The spermine co-matrices are more effective than the spermidine co-matrices, but adduction problems with the spermine co-matrices limits their overall utility. In general, polyamine co-matrices are found to be more effective than monofunctional amine co-matrices at improving the mass spectral data obtained during MALDI-MS of oligonucleotides.

Investigation of the actions and antagonist activity of some polyamine analogues in vivo.[Pubmed:9641557]

Br J Pharmacol. 1998 May;124(2):386-90.

1. The ability of three putative polyamine antagonists to antagonize behavioural changes induced by spermine was assessed. 2. Injection of an excitotoxic dose of spermine (100 microg, i.c.v.) in mice results in the development of a characteristic behavioural profile, which has two temporally distinct phases. The early events include clonic convulsions, and the later, more general excitation, includes tremor and culminates in the development of a fatal tonic convulsion. 3. Co-administration of arcaine (25 microg, i.c.v.) potentiated the early phase effects after spermine injection, but antagonized the development of spermine-induced tonic convulsions. A larger dose of arcaine (50 microg, i.c.v.) given alone resulted in the development of spermine-like body tremor and convulsions. It therefore appears that arcaine is not a pure polyamine antagonist in vivo, but may be a partial agonist. 4. Similarly, 1,10-diaminodecane appeared to act as a partial agonist in vivo, although it was less potent than arcaine. 5. In contrast, diethylenetriamine (DET) effectively inhibited the development of the early effects of spermine, but was ineffective against the spermine-induced CNS excitation and tonic convulsions. 6. It is concluded that none of the putative polyamine antagonists tested behaved as effective polyamine antagonists in vivo, although each produced some antagonism.

Modulation of channel function by polyamines.[Pubmed:8789355]

Trends Pharmacol Sci. 1996 Jan;17(1):22-7.

Polyamines are found in every cell of the body and the intricate enzymatic reactions responsible for their metabolism and transport in mammalian cells are now well understood. Despite intense efforts, elucidation of the role of polyamines has suffered in that little information of physiological relevance has surfaced. Recently, recombinant receptor techniques and increased availability of polyamine analogues have revealed, as discussed here by David Johnson, modulation of NMDA receptors by polyamines by reversal of tonic proton inhibition, and a function for these compounds as 'intrinsic rectifier factors' for K+ channels.

Multiple effects of spermine on N-methyl-D-aspartic acid receptor responses of rat cultured hippocampal neurones.[Pubmed:8229795]

J Physiol. 1993 May;464:131-63.

1. The modulation by polyamines of responses to N-methyl-D-aspartic acid (NMDA) was studied using a rapid perfusion system and whole-cell voltage-clamp recording from rat hippocampal neurons in dissociated culture. 2. Concentration jump responses to 100 microM NMDA in the presence of 10 microM glycine revealed potentiation by 3 mM spermine at a membrane potential of +60 mV, but depression at -120 mV; the degree of potentiation at +60 mV was variable from cell to cell while marked depression at -120 mV was observed in all cells. The depression of responses to NMDA by spermine was highly voltage dependent (z delta = 1.17) with an apparent equilibrium dissociation constant for block at 0 mV of 27 mM. 3. Analysis of spermine dose-potentiation curves for responses recorded at +60 mV in the presence of 10 microM glycine revealed a half-maximal effect at 125 microM. Under the same conditions, but at -60 mV, analysis of spermine-evoked depression was performed for cells with less than 5% potentiation at +60 mV, and revealed half-maximal inhibition at 344 microM. 4. Dose-response analysis for the glycine-sensitive activation of NMDA receptors at +60 mV revealed a 3.5-fold increase in apparent affinity for glycine in the presence of 1 mM spermine. This increase in affinity for glycine was accompanied by a 3.3-fold decrease in the rate of development of glycine-sensitive desensitization, and a 2.4-fold decrease in the rate of dissociation of glycine from NMDA receptors, while the rate constant for dissociation of NMDA was not reduced. 5. In the presence of non-saturating concentrations of glycine, spermine-induced potentiation at +60 mV developed with two exponential components: a slow glycine-sensitive component, the amplitude and time constant of which decreased with increasing glycine concentration (30 nM glycine, amplitude = 80.2 +/- 5.1%, tau = 780 +/- 79 ms; 3 microM glycine, amplitude = 22.6 +/- 7.1%, tau = 45 +/- 13 ms), and a faster component (tau < 20 ms at all concentrations of glycine), the amplitude of which varied from cell to cell, and which became larger with increase in concentration of glycine. When responses to the application of spermine were measured in the presence 10 microM L-alanine instead of 100 nM glycine, the slow component of potentiation was absent.(ABSTRACT TRUNCATED AT 400 WORDS)

Polyamines modulate the neurotoxic effects of NMDA in vivo.[Pubmed:8358608]

Brain Res. 1993 Jul 9;616(1-2):163-70.

The ability of polyamines to alter NMDA-induced neurotoxicity in neonatal rats was examined to determine whether polyamines modulate NMDA receptor activity in vivo. Unilateral injections of NMDA and/or polyamines were made into the striatum of 7-day-old rats. After 5 days, the brains were removed and 20 microns thick coronal sections were cut and stained with Cresyl violet. A computer-based image analysis system was used to densitometrically measure the cross-sectional area of intact tissue in the control and injected hemispheres. Administration of NMDA (5-40 nmol) produced a dose-dependent tissue damage that ranged from 7 to 52% of the area of the uninjected hemisphere. The polyamine agonist spermine (10-500 nmol) dose-dependently exacerbated the toxicity of a 15 nmol dose of NMDA, increasing the size of the lesion by up to 50%. Administration of spermine alone produced dose-dependent tissue damage that ranged from 9 to 52%. The damage produced by both NMDA and spermine could be completely inhibited by co-administration of the NMDA antagonist MK-801. The polyamine inverse agonist 1,10-diaminodecane (DA-10, 50-400 nmol) inhibited the damage produced by NMDA in a dose-dependent manner, with a maximal inhibition of 50%. Administration of DA-10 alone produced limited damage at doses above 100 nmol. The weak partial agonist diethylenetriamine had no effect by itself or on NMDA-induced toxicity at the doses tested. These results indicate that polyamines can modulate the activity of NMDA receptors in vivo and suggest that polyamines or related compounds may have important therapeutic potential as neuroprotective agents.