Histamine Receptor Binding Research Articles

The prefrontal cortex shows widespread decrease in H3 histamine receptor binding densities in rats with genetic generalized epilepsies

Reduced H3 histamine receptor binding densities in the upper layers of motor cortex in rats prone to audiogenic convulsive seizures

Very high frequency versus low & high frequency Subthalamic Deep Brain Stimulation on gait in Parkinson’s disease: A preliminary study

H1 histamine receptor densities are increased in brain regions of rats with genetically generalized epilepsies

CSIR Biosciences interactions with traditional health practitioners led to the identification of a plant, Siphonochilus aethiopicus, commonly known as African ginger. It is one of the most widely used medicinal plants in South Africa, for managing allergic diseases such as colds, influenza and sinus problems. Scientific research conducted, demonstrated the beneficial properties of the plant extract and led to the discovery of the active ingredient, a non-steroidal compound. The plant extract and/or the purified non-steroidal metabolite showed activity in the glucocorticoid receptor, histamine receptor and nuclear factor-κB binding assays as well as the phosphodiesterase IV and 5-lipoxygenase enzymatic assays [2]. All these systems play a crucial role in allergic diseases and inflammation.The organic extract of the rhizomes of the plant demonstrated reduced infiltration of inflammatory cells in the lung tissue of animals in an in vivo anti-asthmatic ovalbumin-sensitized mice assay. These effects were comparable to dexamethasone, a corticosteroid commonly used in clinical practice [2]. The organic extracts given orally to rats, did not show any evident signs of toxicity at the test concentrations of 300 – 2000 mg/kg. Collectively, all the pre-clinical results demonstrated the beneficial properties of the plant extract in the improvement of the symptomatology associated with allergic and infectious diseases and provides scientific evidence substantiating its traditional use and inclusion in complementary medicine products. The CSIR was granted a PCT for use of the extract and compound [1] (PCT/IB2007/050649). Different areas in South Africa have already been identified as ideal sites where cultivation programmes have been initiated for the plant species. As there is currently no clinical evidence of its safety and efficacy, the CSIR obtained approval by the Medical Control Council in South Africa to conduct a Phase IA Clinical, Tolerability study this year.

G-Protein Coupled Receptors (GPCRs) have enormous physiological and biomedical importance, being the primary target of a large number of modern drugs. The availability of structural information of the binding site of the targeted GPCR plays a key role in rationalization, efficiency and cost-effectiveness of the drug discovery process. However, obtaining structural information on GPCRs using X-ray crystallography or NMR requires a large investment of time and is technically very challenging. This situation significantly limits the ability of these methods to have an impact in drug discovery for GPCR targets in the short term and hence there is an urgent need for other effective and cost-efficient alternatives. We present here a practical approach that integrates GPCR modelling with fragment based screening to provide structural insights on the H3 and H4 histamine receptor binding sites. This approach creates a cost-efficient new avenue for structure-based drug design (SBDD) against GPCR targets. We report here a success of using this protocol for the discovery of selective and dual H3 and H4 antagonists. Our fragment screen yielded 44 H3, 21 H4 selective and 20 dual fragment hits. These fragments were used to construct high- quality H3 and H4 models followed by binding site exploration and structure based virtual screening (VS). Overall, 172 compounds were purchased for testing based on the virtual screening results. Of the 74 compounds predicted to have dual activity, 33 had activity against one or other of the two receptors (44%), of which 17 had activity against both. Of the 19 compounds predicted to be H3 selective, 13 were active against H3 (68%) and 10 of these also had selectivity over H4. Of the 79 compounds predicted to be H4 selective, 36 were active against H4 (45%) and 2 of these also had selectivity over H3

The purpose of this review is to evaluate the effect of histamine on various receptors in the conjunctiva. A Medline search from 1980 was performed on the histamine receptor subtypes H1, H2 and H3 in the human conjunctiva. In the conjunctiva, histamine has been shown to induce various physiological and immunological changes through both H1 and H2 receptor stimulation. Histamine binding to conjunctival H1 receptors through the phospholipase C-dependent inositol phosphate pathway leads to the symptom of pruritus while histamine stimulation of the conjunctival H2 receptors has been indirectly shown to cause vasodilation. The effect of histamine on conjunctival H1 receptors appears to be the primary target for ocular allergy treatment as it is primarily involved in ocular pruritus. The exact interaction of the conjunctival H2 receptors appears to work in a complementary fashion to the H1 receptor in controlling other features of ocular allergy such as vasodilation and injection. Thus, oral and topical antihistamines with multiple histamine receptor binding activities may provide an improved treatment paradigm for the various signs and symptoms of ocular allergy. The histamine H1, H2 and H3 receptor affinities of ketotifen, pyrilamine, and epinastine appear to have the strongest H1 and H2 affinities.

Histamine H 1 receptors in patients with Alzheimer’s disease assessed by positron emission tomography

Inhibitory effects of meta-iodo-benzylguanidine (MIBG) on endothelial histamine receptor binding

We have purified a small, basic protein with high affinity and selectivity for biogenic amine receptors to apparent homogeneity from the venom of Russell's viper (Vipera russelli). This protein, which we designate "vipoxin," has Mr = 13,000, and appears to exist in solution as a single polypeptide chain. It may contain 2 atypical amino acids. Vipoxin inhibits in a dose-dependent manner the binding of 3H-ligands to biogenic amine receptors, with apparent Ki values of 3 nM at alpha 1-adrenergic receptors, 5 nM at alpha 2-adrenergic receptors, 15 nM at dopamine receptors, and 32 nM at serotonin receptors. At concentrations up to 1 microM, vipoxin is inactive at beta-adrenergic, histamine, nicotinic cholinergic, muscarinic cholinergic, adenosine, gamma-aminobutyric acid, benzodiazepine, or opiate receptor binding sites. The effect of vipoxin is essentially irreversible over 20 h at alpha 1- and alpha 2-adrenergic receptors and serotonin receptors and is only slightly reversible at dopamine receptors. Norepinephrine protects alpha-adrenergic receptors from inhibition by vipoxin, while dopamine does not. Vipoxin has no protease activity but does have phospholipase A2 activity, which cannot account for its action on receptors, since receptor binding is assayed in the presence of 1 mM CoSO4 which completely and selectively inhibits the phospholipase activity. Other phospholipases A2 in the same venom lack vipoxin's action on receptors. In physiologic experiments, vipoxin behaves as an agonist at alpha 2-adrenergic receptors in the rat vas deferens and is over an order of magnitude more potent than norepinephrine itself. At alpha 1-adrenergic receptors, it is neither a simple agonist nor an antagonist, but selectively potentiates norepinephrine. Vipoxin may be a useful tool for biogenic amine receptor characterization.