Epinastine (WAL 801CL) modulates the noncholinergic contraction in guinea-pig airways in vitro by a prejunctional 5-HT1-like receptor.
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Dupont LJ, Meade CJ, Demedts MG, Verleden GM
Epinastine (WAL 801CL) modulates the noncholinergic contraction in guinea-pig airways in vitro by a prejunctional 5-HT1-like receptor.
Eur Respir J. 1996 Jul;9(7):1433-8.
- PubMed ID
- 8836655 [ View in PubMed]
- Abstract
Electrical field stimulation (EFS) of guinea-pig airways, in vitro, evokes an excitatory nonadrenergic noncholinergic (eNANC) contraction mediated by release of tachykinins from sensory nerve endings. Epinastine (WAL 801CL) is an antihistaminic drug with binding affinity at certain other receptors, including alpha-adrenergic receptors and various serotonin (5-HT) receptor subtypes. It is used in asthma treatment; however, its mechanism of action remains to be fully defined. We have investigated whether epinastine could modulate the eNANC contraction in guinea-pig airways in vitro, and have tried to elucidate its receptor mechanism. Epinastine (0.1-100 microM) produced a concentration-dependent inhibition of the noncholinergic contraction, with a maximum inhibition of 91 +/- 7% at 100 microM. Pretreatment of the tissues with combined 5-HT1/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction. Pretreatment with tropisetron (1 microM), a 5-HT3 antagonist, ketanserin (10 microM), a 5-HT2 antagonist, thioperamide (10 microM), a histamine H3 antagonist, or phentolamine (10 microM), an alpha-adrenergic antagonist, however, had no effect. Chlorpheniramine (10 microM), another histamine H1 receptor antagonist without significant 5-HT receptor binding affinity, did not produce any inhibition of the eNANC contraction. Epinastine (100 microM) did not displace the dose-response curve to exogenously applied substance P (0.01-10 microM). These results suggest that epinastine, although identified as a 5-HT antagonist, acts as a 5-HT1 agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional 5-HT1-like receptor, located to sensory nerves.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Epinastine 5-hydroxytryptamine receptor 2A Protein Humans UnknownAntagonistDetails Epinastine Alpha-1A adrenergic receptor Protein Humans UnknownUnknownDetails Epinastine Alpha-2A adrenergic receptor Protein Humans UnknownUnknownDetails