(+/-)-6-Methyl-5,6,7,8-Tetrahydropterine Dihydrochloride

• CAS: 69113-63-9
• Catalog Number: ACM69113639-1
• Category: Main Products
• Molecular Weight: 254.12
• Molecular Formula: C7H13Cl2N5O
• Synonyms: 2-amino-6-methyl-5,6,7,8-tetrahydro-3H-pteridin-4-one;dihydrochloride
• Appearance: Off-white powder

Case Study

Circadian Rhythms of Hepatic Serotonin Metabolism Revealed Using 6-Methyl-Tetrahydropterine as a Tryptophan Hydroxylase Cofactor

Valdés-Fuentes, Marlen, et al. Physiological Reports 3.5 (2015): e12389.

Serotonin is a critical signaling molecule in the gastrointestinal tract, platelets, and nervous system, yet its daily metabolic fluctuations in the liver remained unexplored. This study established the first 24-hour profile of hepatic serotonin synthesis and degradation in rats, employing 6-methyl-5,6,7,8-tetrahydropterine dihydrochloride (6-MPH₄) as the essential cofactor in a radiometric tryptophan hydroxylase (TPH) activity assay.
Experimental Protocol: Adult male Wistar rats were maintained under 12:12 hour light-dark cycles and divided into four groups: ad libitum feeding, daytime restricted feeding (DRF; 2-hour access from 1200-1400 for 3 weeks), acute 21-hour fasting, and fasting-refeeding. Liver samples were collected at eight time points across 24 hours. Serotonin, 5-hydroxytryptophan, and L-tryptophan were quantified by HPLC with electrochemical detection. TPH-1 enzymatic activity was measured using a radioactive isotope assay with 6-MPH₄ at 500 micromolar as the co-substrate. Western blotting, qPCR, and immunohistochemistry assessed TPH-1 and monoamine oxidase A expression.
Performance Evaluation: In ad libitum fed animals, liver serotonin, TPH-1 activity, TPH-1 protein abundance, and blood serotonin levels exhibited synchronized circadian rhythms peaking at 0800 hours (light onset). The DRF protocol severely disrupted this coordination: TPH-1 activity at 0800 hours was significantly blunted, hepatic serotonin dropped during the light period, and serum 5-HT showed an inverted anti-phase rhythm. Platelet counts remained unchanged, indicating that the rhythm disturbance originated from altered serotonin uptake and release kinetics rather than platelet number changes. These findings demonstrate that 6-MPH₄-dependent TPH-1 activity is a key circadian-regulated node in peripheral serotonin homeostasis.

Subtype-Specific Alpha-2 Adrenergic Control of Adrenal Catecholamine Release Elucidated with 6-Methyl-Tetrahydropterine

Vieira-coelho, Maria, et al. British Journal of Pharmacology (2009).

The adrenal medulla releases noradrenaline and adrenaline into circulation through tightly regulated exocytosis, but the specific alpha-2 adrenoceptor subtypes mediating negative feedback inhibition were poorly defined. This investigation pharmacologically characterized the receptor subtypes in murine adrenal medulla using selective agonists, antagonists, and genetically modified mouse models, with 6-methyl-5,6,7,8-tetrahydropterine dihydrochloride (6-BH₄) serving as the cofactor in tyrosine hydroxylase kinetic assays.
Experimental Protocol: Isolated adrenal medullae from wild-type and alpha-2A, alpha-2B, and alpha-2C knockout mice were placed in superfusion chambers. Catecholamine overflow was evoked by the nicotinic agonist DMPP (500 micromolar) in the presence or absence of the alpha-2 agonist medetomidine and various antagonists (rauwolscine, phentolamine, prazosin, spiroxatrine, WB4101). Tyrosine hydroxylase activity was determined using saturation curves with L-tyrosine as substrate and 6-BH₄ (10-1000 micromolar) as cofactor. Catecholamines were assayed by HPLC with electrochemical detection.
Performance Evaluation: Medetomidine inhibited noradrenaline and adrenaline overflow with EC₅₀ values of 1.5 and 1.9 nanomolar, respectively, and maximal inhibition exceeding 90%. Antagonist pK_D correlations identified the alpha-2C subtype as the predominant autoreceptor for adrenaline release, confirmed by a drastic reduction of medetomidine effect (only 14% inhibition remaining) in alpha-2C knockout mice. In contrast, all three subtypes contributed equally to noradrenaline release control. Tyrosine hydroxylase kinetic parameters (V_max and K_M for both substrate and 6-BH₄) were unchanged across genotypes, indicating that altered release rather than synthesis accounted for the phenotype. The alpha-2C subtype thus represents a selective pharmacological target for modulating adrenomedullary adrenaline output.

Custom Q&A

What is the molecular formula of (+/-)-6-Methyl-5,6,7,8-Tetrahydropterine Dihydrochloride?

The molecular formula is C7H13Cl2N5O.

What are the synonyms of (+/-)-6-Methyl-5,6,7,8-Tetrahydropterine Dihydrochloride?

The synonyms are 69113-63-9, (+/-)-6-Methyl-5,6,7,8-tetrahydropterine dihydrochloride, 2-Amino-6-methyl-5,6,7,8-tetrahydropteridin-4(1H)-one dihydrochloride, and more.

What is the molecular weight of (+/-)-6-Methyl-5,6,7,8-Tetrahydropterine Dihydrochloride?

The molecular weight is 254.11 g/mol.

What is the parent compound of (+/-)-6-Methyl-5,6,7,8-Tetrahydropterine Dihydrochloride?

The parent compound is 6-Methyltetrahydropterin.

What are the component compounds of (+/-)-6-Methyl-5,6,7,8-Tetrahydropterine Dihydrochloride?

The component compound is 6-Methyltetrahydropterin and Hydrochloric Acid.

What is the InChI of (+/-)-6-Methyl-5,6,7,8-Tetrahydropterine Dihydrochloride?

The InChI is InChI=1S/C7H11N5O.2ClH/c1-3-2-9-5-4(10-3)6(13)12-7(8)11-5;;/h3,10H,2H2,1H3,(H4,8,9,11,12,13);2*1H

What is the InChIKey of (+/-)-6-Methyl-5,6,7,8-Tetrahydropterine Dihydrochloride?

The InChIKey is MKQLORLCFAZASZ-UHFFFAOYSA-N.

What is the Canonical SMILES of (+/-)-6-Methyl-5,6,7,8-Tetrahydropterine Dihydrochloride?

The Canonical SMILES is CC1CNC2=C(N1)C(=O)NC(=N2)N.Cl.Cl.

What is the CAS number of (+/-)-6-Methyl-5,6,7,8-Tetrahydropterine Dihydrochloride?

The CAS number is 69113-63-9.

What is the hydrogen bond acceptor count of (+/-)-6-Methyl-5,6,7,8-Tetrahydropterine Dihydrochloride?

The hydrogen bond acceptor count is 4.