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At least 127 records · Page 7Linked to original sources
PubMed1990

A study of the necrotic actions of the venom of the wolf spider, Lycosa godeffroyi, on mouse skin.

1. The venom of the wolf spider, Lycosa godeffroyi, caused cutaneous necrosis when injected into mice. 2. A strong inflammatory response and total loss of epidermal cellularity were features of this in vivo necrosis. 3. Mouse skin envenomated while in tissue culture showed epidermal detachment and reduced cellular adhesion. 4. Triprolidine and methysergide, used together, indomethacin, heparin and human and mouse sera all failed to inhibit the necrosis significantly. 5. The venom caused moderate haemolysis, complement consumption and inhibition of clotting, these apparently not being the main reasons for the necrosis. 6. Neither Atrax infensus venom nor hyaluronidase caused similar epithelial damage.

Animals↗
PubMed2006

Histamine improves rat rota-rod and balance beam performances through H(2) receptors in the cerebellar interpositus nucleus.

Previous studies have revealed a direct histaminergic projection from the tuberomamillary nucleus of hypothalamus to the cerebellum and a postsynaptic excitatory effect of histamine on the cerebellar interpositus nucleus neurons via histamine H(2) receptors in vitro, indicating that the histaminergic afferent inputs of cerebellar nuclei may be involved in the cerebellar function of motor control. To test this hypothesis, in this study histaminergic agents were bilaterally microinjected into the cerebellar interpositus nucleus of intact adult male rats, and their effects on motor balance and coordination of the animals performing accelerating rota-rod treadmill and balance beam tasks were observed. The results showed that microinjection of histamine into the cerebellar interpositus nucleus remarkably increased the time that animals balanced steadily on the rota-rod and markedly shortened the duration of passage through the balance beam, whereas GABA significantly depressed motor performances of animals on the rota-rod and beam, and normal saline influenced neither. In addition, administration of selective histamine H(2) receptor antagonist ranitidine considerably decreased the animals' endurance time on rota-rod and noticeably increased the passing time on beam, but selective histamine H(1) receptor antagonist triprolidine showed no effect. Furthermore, microinjection of histamine reversed the inhibitory effects of ranitidine on rota-rod and beam performance. These results demonstrate that histamine enhances rat motor balance and coordination through activation of histamine H(2) receptors in the cerebellar interpositus nucleus and suggest that the hypothalamocerebellar histaminergic projections may play a modulatory role on the cerebellar circuitry to ensure that movements are accurately executed.

Action Potentials↗
PubMed2000

Antihistamine terfenadine potentiates NMDA receptor-mediated calcium influx, oxygen radical formation, and neuronal death.

We previously reported that the histamine H1 receptor antagonist terfenadine enhances the excitotoxic response to N-methyl-D-aspartate (NMDA) receptor agonists in cerebellar neurons. Here we investigated whether this unexpected action of terfenadine relates to its antihistamine activity, and which specific events in the signal cascade coupled to NMDA receptors are affected by terfenadine. Low concentrations of NMDA (100 microM) or glutamate (15 microM) that were only slightly (<20%) toxic when added alone, caused extensive cell death in cultures pre-exposed to terfenadine (5 microM) for 5 h. Terfenadine potentiation of NMDA receptor response was mimicked by other H1 antagonists, including chlorpheniramine (25 microM), oxatomide (20 microM), and triprolidine (50 microM), was prevented by histamine (1 mM), and did not require RNA synthesis. Terfenadine increased NMDA-mediated intracellular calcium and cGMP synthesis by approximately 2.4 and 4 fold respectively. NMDA receptor-induced cell death in terfenadine-treated neurons was associated with a massive production of hydrogen peroxides, and was significantly inhibited by the application of either (+)-alpha-tocopherol (200 microM) or the endogenous antioxidant melatonin (200 microM) 15 min before or up to 30 min after receptor stimulation. This operational time window suggests that an enduring production of reactive oxygen species is critical for terfenadine-induced NMDA receptor-mediated neurodegeneration, and strengthens the importance of antioxidants for the treatment of excitotoxic injury. Our results also provide direct evidence for antihistamine drugs enhancing the transduction signaling activated by NMDA receptors in cerebellar neurons.

Animals↗
PubMed1984

Management of middle-ear effusions in children.

A double-blind placebo controlled trial of Mucodyne (carbocisteine, Berk Pharmaceuticals), Actifed (triprolidine HC1 and pseudoephedrine HC1, Wellcome) and combined Mucodyne and Actifed in the treatment of middle-ear effusions is reported. The trial was undertaken to assess whether either preparation, alone or in combination, would reduce the number of children requiring surgical treatment for this condition. No statistical difference between the various groups in avoiding surgical treatment was detected. In those patients undergoing surgery, pre-operative treatment with Mucodyne was associated with a significantly greater number of ears restored to a normal appearance and middle ear function as measured by tympanometry. All patients relapsing after surgery belonged to the groups receiving placebo, Actifed or the combination of Mucodyne and Actifed prior to the operation.

Carbocysteine↗
PubMed2002

Endogenous histamine in the medial septum-diagonal band complex increases the release of acetylcholine from the hippocampus: a dual-probe microdialysis study in the freely moving rat.

The effects of histaminergic ligands on both ACh spontaneous release from the hippocampus and the expression of c-fos in the medial septum-diagonal band (MSA-DB) of freely moving rats were investigated. Because the majority of cholinergic innervation to the hippocampus is provided by MSA-DB neurons, we used the dual-probe microdialysis technique to apply drugs to the MSA-DB and record the induced effects in the projection area. Perfusion of MSA-DB with high-KCl medium strongly stimulated hippocampal ACh release which, conversely, was significantly reduced by intra-MSA-DB administration of tetrodotoxin. Histamine or the H2 receptor agonist dimaprit, applied directly to the hippocampus, failed to alter ACh release. Conversely, perfusion of MSA-DB with these two compounds increased ACh release from the hippocampus. Also, thioperamide and ciproxifan, two H3 receptor antagonists, administered into MSA-DB, increased the release of hippocampal ACh, whereas R-alpha-methylhistamine, an H3 receptor agonist, produced the opposite effect. The blockade of MSA-DB H2 receptors, caused by local perfusion with the H2 receptor antagonist cimetidine, moderated the spontaneous release of hippocampal ACh and antagonized the facilitation produced by H3 receptor antagonists. Triprolidine, an H1 receptor antagonist, was without effect. Moreover, cells expressing c-fos immunoreactivity were significantly more numerous in ciproxifan- or thioperamide-treated rats than in controls, although no colocalization of anti-c-fos and anti-ChAT immunoreactivity was observed. These results indicate a role for endogenous histamine in modulating the cholinergic tone in the hippocampus.

Acetylcholine↗
PubMed1999

Mutational analysis of the antagonist-binding site of the histamine H(1) receptor.

We combined in a previously derived three-dimensional model of the histamine H(1) receptor (Ter Laak, A. M., Timmerman, H., Leurs, H., Nederkoorn, P. H. J., Smit, M. J., and Donne-Op den Kelder, G. M. (1995) J. Comp. Aid. Mol. Design. 9, 319-330) a pharmacophore for the H(1) antagonist binding site (Ter Laak, A. M., Venhorst, J., Timmerman, H., and Donné-Op de Kelder, G. M. (1994) J. Med. Chem. 38, 3351-3360) with the known interacting amino acid residue Asp(116) (in transmembrane domain III) of the H(1) receptor and verified the predicted receptor-ligand interactions by site-directed mutagenesis. This resulted in the identification of the aromatic amino acids Trp(167), Phe(433), and Phe(436) in transmembrane domains IV and VI of the H(1) receptor as probable interaction points for the trans-aromatic ring of the H(1) antagonists. Subsequently, a specific interaction of carboxylate moieties of two therapeutically important, zwitterionic H(1) antagonists with Lys(200) in transmembrane domain V was predicted. A Lys(200) --> Ala mutation results in a 50- (acrivastine) to 8-fold (d-cetirizine) loss of affinity of these zwitterionic antagonists. In contrast, the affinities of structural analogs of acrivastine and cetirizine lacking the carboxylate group, triprolidine and meclozine, respectively, are unaffected by the Lys(200) --> Ala mutation. These data strongly suggest that Lys(200), unique for the H(1) receptor, acts as a specific anchor point for these "second generation" H(1) antagonists.

Animals↗
PubMed1967

Complement as a mediator of inflammation. II. Biological properties of anaphylatoxin prepared with purified components of human complement.

Interaction in free solution of highly purified preparations of human C'1 esterase, C'4, C'2, and C'3, in the presence of Mg(2+), resulted in rapid generation of an activity indistinguishable by biological criteria from anaphylatoxin. The formation of anaphylatoxin was associated with immunoelectrophoretic conversion of C'3 to anodically faster migrating proteins and was unaffected by the presence or absence of added C'5. The biological properties of human anaphylatoxin prepared in this manner include: contraction and desensitization of isolated guinea pig ileum, failure to contract isolated rat uterus, enhancement of vascular permeability in guinea pig skin, degranulation of mast cells in guinea pig mesentery preparations, and liberation of histamine from suspensions of rat peritoneal mast cells. The smooth muscle-contracting and permeability enhancing properties were fully blocked by an antihistaminic drug, triprolidine. No cross-desensitizing activity on guinea pig ileum was demonstrable between rat and human or guinea pig and human anaphylatoxins but a closer biological relationship between rat and guinea pig anaphylatoxins was observed. It is concluded that anaphylatoxin is a product of the complement system. Its possible relationship to apparently similar activities currently being obtained in other laboratories has been discussed.

Anaphylaxis↗
PubMed1979

Antihistamines and alpha-adrenergic agents in treatment of otitis media.

Studies are not available to support the common use of alpha-adrenergic agents and/or antihistamines in the treatment of acute otitis media. A total of 378 patients with acute otitis were entered in a double-blind study comparing treatment results with antibiotics and either placebo, pseudoephedrine, triprolidine, or a combination of these; 196 patients returned. Age and return rate did not differ among groups. Cure rates and duration of fever were the same for each group. The cost and possible side effects of these agents, added to their lack of beneficial effect in otitis, should interdict their use.

Clinical Trials as Topic↗
PubMed1984

Visual motor co-ordination and dynamic visual acuity.

Data on the effect of an antihistamine (triprolidine 10 mg) on visuo-motor coordination and dynamic visual acuity were used to establish interactions between these skills. Analysis of covariance and principal component analysis were used. The analyses suggested two main effects--an effect on the activity of the neuromuscular system and one which impaired ability to anticipate target movement. Detection of impaired performance by any task may have wider implications to the effectiveness of the individual than that obviously suggested by the skill itself.

Humans↗
PubMed1986

Effects of a mu-opioid receptor agonist (codeine phosphate) on visuo-motor coordination and dynamic visual acuity in man.

Effects of codeine (30, 60 and 90 mg) on visuo-motor coordination and dynamic visual acuity, together with critical flicker fusion, digit symbol substitution, complex reaction time and subjective assessments of mood, were studied from 0.75-2.0 h after ingestion by six healthy female adults. The study was double-blind and placebo controlled, and triprolidine (10 mg) was used as the active control. The effect on visuo-motor coordination was limited and was dose related and linear, and performance was altered on visuo-motor coordination with 60 and 90 mg codeine, and on dynamic visual acuity with 90 mg codeine (P less than 0.05). No other effect of codeine was detected. Modulated neuromuscular function is likely to be the common denominator of the changes in performance with codeine, though nausea, but not sedation, may be a contributory factor. It is possible that altered performance with codeine may involve interactions with different receptors than those which lead to sedation.

Adult↗
PubMed1989

Pharmacological control of the human gastric histamine H2 receptor by famotidine: comparison with H1, H2 and H3 receptor agonists and antagonists.

Histamine 0.1 microM-0.1 mM increased adenylate cyclase activity five- to ten-fold in human fundic membranes, with a potency Ka = 3 microM. The histamine dose-response curve was mimicked by the H3 receptor agonist (R) alpha-MeHA, but at 100 times lower potency, Ka = 0.3 mM. Histamine-induced adenylate cyclase activation was abolished by H2, H1 and H3 receptor antagonists, according to the following order of potency IC50: famotidine (0.3 microM) greater than triprolidine (0.1 mM) thioperamide (2 mM), respectively. Famotidine has no action on membrane components activating the adenylate cyclase system, including the Gs subunit of the enzyme stimulated by forskolin and cell surface receptors sensitive to isoproterenol (beta 2-type), PGE2 and VIP. The Schild plot was linear for famotidine (P less than 0.01) with a regression coefficient r = 0.678. The slope of the regression line was 0.64 and differs from unity. Accordingly, famotidine showed a slow onset of inhibition and dissociation from the H2 receptor in human cancerous HGT-1 cells. The results demonstrate that famotidine is a potent and selective H2 receptor antagonist with uncompetitive actions in human gastric mucosa. Consequently, famotidine might be a suitable drug with long-lasting actions in the treatment of Zollinger-Ellison syndrome. The results also confirm and extend the previous observations that (R) alpha-MeHA and thioperamide are two selective ligands at histamine H3 receptor sites. In the human gastric mucosa, these drugs are respectively 330 and 6700 times less potent than histamine and famotidine on the adenylate cyclase system. The possible involvement of histamine H3 receptors in the regulation of gastric secretion is proposed.

Adenylyl Cyclases↗
PubMed1995

Antihistamine effects on actual driving performance in a standard test: a summary of Dutch experience, 1989-94.

The review summarizes the major results of eight double-blind, placebo-controlled, volunteer studies undertaken by three independent institutions for showing the effects on actual driving performance of "sedating" and "nonsedating" antihistamines (respectively, triprolidine, diphenhydramine, clemastine and terfenadine, loratadine, cetirizine, acrivastine, mizolastine, and ebastine). A common, standardized test was used that measures driving impairment from vehicular "weaving" (i.e., standard deviation of lateral position (SDLP)). Logical relationships were found between impairment and dose, time after dosing, and repeated doses over 4-5 days. The newer drugs were generally less impairing, but differences existed among their effects, and none was unimpairing at doses 1-2x the currently recommended levels. One or possibly two of the newer drugs possessed both performance-enhancing and -impairing properties, depending on dose, suggesting two mechanisms of action.

Automobile Driving↗
PubMed1994

Regulation of K+ conductance by histamine H1 and H2 receptors in neurones dissociated from rat neostriatum.

1. The effects of histamine on dissociated neostriatal neurones of the rat were investigated in the whole-cell mode using the nystatin-perforated patch recording technique. 2. Histamine evoked a net inward current accompanied by a decrease in the membrane conductance at a holding potential (Vh) of -44 mV. This response was observed in neurones considered to be interneurones based on morphology, membrane properties and the responsiveness to acetylcholine. 3. A net inward current evoked by 10(-8) to 10(-6) M histamine was inhibited in a concentration-dependent manner by the H1 receptor antagonists, pyrilamine and triprolidine. The H1 receptor agonists, 2-methylhistamine and 2-thiazolylethylamine, mimicked the histamine response, indicating that this response was mediated by the H1 receptor. 4. Histamine, at high concentrations between 10(-6) and 10(-5) M, evoked an additional net inward current with a decrease in the membrane conductance, which was inhibited by the H2 receptor antagonists, cimetidine, ranitidine and famotidine. The H2 receptor agonist, impromidine, partially mimicked the response. Thus, this additional current was considered to be mediated by the H2 receptor. 5. The reversal potentials for H1 and H2 receptor-operated currents shifted 56.9 and 59.3 mV for a 10-fold change in [K+]o, respectively, suggesting that these currents were carried by K+. 6. An analysis of change in current fluctuations mediated by H1 and H2 receptors suggested that the unitary current amplitudes of K+ channels linked to H1 and H2 receptors were 0.29 +/- 0.06 (n = 4) and 0.27 +/- 0.07 pA (n = 4), respectively. There was no significant difference between these values. The estimated mean life times (tau) for both channels were also identical (1.1 ms). 7. It was concluded that histamine reduces K+ currents in neostriatal interneurones and that both H1 and H2 receptors are involved in the response.

Animals↗
PubMed1996

Histamine-sensitive intrinsic cardiac and intrathoracic extracardiac neurons influence cardiodynamics.

Studies were performed to determine whether 1) histamine can modify the spontaneous activity of mammalian intrinsic cardiac neurons in situ, 2) histamine-sensitive neurons exist in intrathoracic intrinsic cardiac and extracardiac ganglia that are involved in cardiac regulation, and 3) histamine-sensitive intrathoracic cardiac neurons possess H1 or H2 receptors. histamine (10 microliters; 100 microM), when applied adjacent to spontaneously active canine right atrial neurons in situ, increased ongoing activity in some of them. Histamine, when administered into the local arterial blood supply of these neurons (0.1 ml; 100 microM) not only increased their activity but induced cardiac augmentation. Cardioaugmentor responses were also elicited when histamine (10 microliters or 0.1 ml; 100 microM) was administered into limited loci within stellate and middle cervical ganglia that were connected to the heart, but not in ganglia surgically disconnected the heart. Neuronal and cardiac responses no longer were elicited after local administration of the H1-selective receptor antagonist triprolidine. They were unaffected by local application of the H2-selective receptor antagonist cimetidine. No cardiac augmentation was elicited when histamine was applied to intrathoracic autonomic neurons following timolol (1 mg/kg i.v.) administration. These data indicate that 1) histaminergic neurons exist in intrinsic cardiac and intrathoracic extracardiac ganglia that are involved in cardiac regulation, 2) these neurons possess H1 receptors, and 3) histamine-sensitive intrathoracic neurons directly or indirectly activate cardiac adrenergic neurons, thereby inducing cardiac augmentation

Animals↗
PubMed2005

Histamine excites neonatal rat sympathetic preganglionic neurons in vitro via activation of H1 receptors.

The role of histamine in regulating excitability of sympathetic preganglionic neurons (SPNs) and the expression of histamine receptor mRNA in SPNs was investigated using whole-cell patch-clamp electrophysiological recording techniques combined with single-cell reverse transcriptase polymerase chain reaction (RT-PCR) in transverse neonatal rat spinal cord slices. Bath application of histamine (100 microM) or the H1 receptor agonist histamine trifluoromethyl toluidide dimaleate (HTMT; 10 microM) induced membrane depolarization associated with a decrease in membrane conductance in the majority (70%) of SPNs tested, via activation of postsynaptic H1 receptors negatively coupled to one or more unidentified K+ conductances. Histamine and HTMT application also induced or increased the amplitude and/or frequency of membrane potential oscillations in electrotonically coupled SPNs. The H2 receptor agonist dimaprit (10 microM) or the H3 receptor agonist imetit (100 nM) were without significant effect on the membrane properties of SPNs. Histamine responses were sensitive to the H1 receptor antagonist triprolidine (10 microM) and the nonselective potassium channel blocker barium (1 mM) but were unaffected by the H2 receptor antagonist tiotidine (10 microM) and the H3 receptor antagonist, clobenpropit (5 microM). Single cell RT-PCR revealed mRNA expression for H1 receptors in 75% of SPNs tested, with no expression of mRNA for H2, H3, or H4 receptors. These data represent the first demonstration of H1 receptor expression in SPNs and suggest that histamine acts to regulate excitability of these neurons via a direct postsynaptic effect on H1 receptors.

Action Potentials↗
PubMed1988

Comparison of the new antihistamine acrivastine (BW 825C) versus cyproheptadine in the treatment of idiopathic cold urticaria.

A double-blind, crossover trial with a new triprolidine derivative, acrivastine (BW 825C; 8 mg 3 times daily), cyproheptadine (4 mg 3 times daily) and placebo was carried out in 18 patients suffering from idiopathic cold urticaria. Acrivastine and cyproheptadine significantly (p less than 0.01) reduced weal areas following ice cube challenge when compared to placebo. Acrivastine was found to be significantly more effective (p less than 0.01) than cyproheptadine in reducing weal areas. Furthermore, cyproheptadine caused significantly more drowsiness than acrivastine (p = 0.021) or placebo (p = 0.013), which did not differ from each other. This study shows that acrivastine is an effective agent in the treatment of cold urticaria and suggests that acrivastine in the dose used lacks adverse effects, such as drowsiness, traditionally associated with antihistamine therapy.

Adult↗