Disease relevance of Benextramine

• Selective blockade and recovery of cell surface alpha 2-adrenergic receptors in human erythroleukemia (HEL) cells. Studies with the irreversible antagonist benextramine [1].
• The presence of benextramine also caused a small tachycardia in both rabbit and guinea pig right atria which was probably due to the release of endogenous noradrenaline [2].
• In low concentrations (0.3-3 muM) the tetramine disulfide benextramine (BHC; N,N'-bis[6-(o-methoxybenzylamino)-n-hexyl]cystamine) potentiated the contracture of the isolated frog rectus abdominis muscle caused by acetylcholine but in the presence of physostigmine or in a higher concentration (10 muM) it inhibited [3].

High impact information on Benextramine

• Femoral arteries were pretreated with benextramine to cause partial alpha-adrenoceptor inactivation [4].
• Furthermore, incubation of islets with benextramine, a selective antagonist of the alpha(2)-AR, restored insulin secretion in response to glucose in isolated islets from transgenic mice, whereas it had no effect on control islets [5].
• Treatment of bovine hippocampal membranes with benextramine inhibited NPY affinity cross-linking to the 50-kDa receptor [6].
• In membranes prepared from HEL cells, benextramine competed for all alpha 2-adrenergic receptors ( [3H]yohimbine sites) [1].
• The recovery of post- and extrasynaptic alpha 2-adrenergic receptor-binding sites was studied in vivo in male golden hamsters after treatment with an irreversible alpha-adrenoceptor antagonist benextramine, a tetramine disulfide that possesses a high affinity for alpha 2-binding sites [7].

Biological context of Benextramine

• The bis(N,N-dialkylguanyl) disulfide and carbon analogs 14a-c were 3-4 times more potent than their respective controls in displacing [3H]NPY from rat brain membrane homogenates with IC50's ranging from 15 to 18 microM and maintained selectivity for the benextramine-sensitive, Y1 binding site population [8].
• Structure-activity relationships among benextramine-related tetraamine disulfides. Chain length effect on alpha-adrenoreceptor blocking activity [9].
• In conscious rabbits the vasoconstriction caused by the nasopharyngeal reflex initiated by smoke inhalation was unaffected by benextramine (10 mg kg-1) [10].
• Inhibition of adrenaline-induced platelet aggregation by the alpha-adrenoceptor blocking drug benextramine [11].
• Under these conditions, the concentration-effect curve to NE remaining after treatment with benextramine showed an IC50 of about 3 X 10(-7) M and an intrinsic activity of 0 [12].

Anatomical context of Benextramine

• Although it bound irreversibly to peripheral and central alpha 2-adrenergic receptors on isolated membranes, benextramine was unable to cross the blood-brain barrier of the hamster at the concentrations used (10-20 mg/kg) [7].
• Alpha 2-adrenergic receptor turnover in adipose tissue and kidney: irreversible blockade of alpha 2-adrenergic receptors by benextramine [7].
• The biosynthesis rate of the receptor was studied in postconfluent HT29 cells, when its density expressed as fmol/mg of cell membrane protein is constant, by following the recovery of the receptor binding capacity after blockade with the non-reversible alpha-adrenergic antagonist benextramine [13].
• Furthermore, it was more specific than benextramine (1) toward the muscarinic receptor, being significantly less potent in inhibiting the carbachol-induced response in rat jejunum [14].
• Discrimination by benextramine between the NPY-Y1 receptor subtypes present in rabbit isolated vas deferens and saphenous vein [15].

Associations of Benextramine with other chemical compounds

• 2 Benextramine irreversibly inhibited the H2-receptor-mediated chronotropic effect of histamine on guinea-pig isolated atrium [16].
• This low-affinity site for NE was also evident after alkylation of alpha adrenoceptors with other irreversibly acting antagonists (e.g., benextramine and dibenamine) [17].
• This immediate and prolonged potentiation was abolished by phentolamine, attenuated by benextramine and the reputed NPY antagonist, PYX1 [18].
• This makes benextramine a most potent Ca2+ blocker compared to verapamil or nicardipine (IC50 = 200 microM and 170 microM, respectively) [19].
• The receptor reserve of G-protein activation and cAMP responses was measured with the irreversible antagonist, benextramine; K(A) values of norepinephrine or UK14,304 were similar (289, 271 or 150, 163 nM, respectively) [20].

Gene context of Benextramine

• Incubation with benextramine (BXT) at 100 microM for 30 min irreversibly abolished the contractile response to [Leu31,Pro34] NPY but was ineffective against NPY18-36-induced contractions [15].
• Failure of the putative neuropeptide Y antagonists, benextramine and PYX-2, to inhibit Y2 receptors in rat isolated prostatic vas deferens [21].
• 2. The putative Y1 and Y2 antagonist, benextramine (BXT), incubated at 100 microM for 10 or 60 min, was ineffective against PYY-induced inhibition of the twitch response, suggesting that the prejunctional Y2 receptor in this tissue is different from the postjunctional one reported in the literature to be sensitive to BXT blockade [21].

Analytical, diagnostic and therapeutic context of Benextramine

• N alpha-Acetyl (Ac), N-terminal deletion fragments of porcine neuropeptide Y (NPY) have been synthesized and characterized for solution conformation properties by circular dichroism and for receptor binding activity at benextramine-sensitive Y1 binding sites in rat brain cortex [22].
• These constrictions were not further reduced by benextramine (1-10 microM), but were abolished by dihydroergotamine (1-10 microM) [23].
• Benextramine noncompetitively inhibited the pressor response to intravenous injection of NPY and the increase in MAP evoked by CCh microinjection into adrenergic and V1-vasopressin receptor-blocked rats, whereas benextramine competitively inhibited the pressor response to angiotensin II (AII) [24].

References