European journal of pharmacology
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Comparative Study
Ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate is a novel positive modulator of GABAA receptors.
Ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate (TG41) enhanced the binding both of gamma-aminobutyric acid (GABA) and of flunitrazepam to rat cerebral cortical membranes. Electrophysiological recordings from Xenopus oocytes expressing various recombinant GABA(A) receptor subtypes revealed that TG41 enhanced the function of all receptor subunit combinations tested. ⋯ This drug induced a reversible loss of the righting reflex in Xenopus tadpoles and it elicited hypnosis (5 mg/kg) after intravenous administration in rats. These results indicate that the pharmacological profile of TG41 is similar to that of general anesthetics which potentiate the activity of GABA(A) receptors containing the beta2 or beta3 subunit.
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Comparative Study
Effects of a 5-HT2A receptor antagonist, sarpogrelate on thermal or inflammatory pain.
The effects of intrathecally and systemically administered 5-hydroxytriptamine (5-HT)(2A) receptor antagonist, sarpogrelate on acute thermal or formalin induced pain were examined. Male Sprague-Dawley rats with lumbar intrathecal catheters were tested with their tail withdrawal response to thermal stimulation (tail flick test) or their paw flinching and shaking response by subcutaneous formalin injection into the hind paw (formalin test) after intrathecal or intraperitoneal administration of sarpogrelate. 5-HT(2A) receptor agonist was used to antagonize the effects of sarpogrelate. In the tail flick test, only intraperitoneal administration induced analgesia. ⋯ Motor disturbance and behavioral side effects were not observed. In conclusion, sarpogrelate might be analgesic on inflammatory induced acute and facilitated pain by intrathecal or systemic administration. However, only systemic administration could be effective on thermal induced acute pain.
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Comparative Study
Comparison of the gastroprokinetic effects of ghrelin, GHRP-6 and motilin in rats in vivo and in vitro.
Ghrelin and motilin form a new family of structurally related peptides. We compared the gastroprokinetic effects of ghrelin, the ghrelin receptor agonist, growth hormone releasing peptide 6 (GHRP-6), and motilin in rats in vivo and in vitro. ⋯ Ghrelin and GHRP-6 but not motilin accelerate gastric emptying and transit by activating cholinergic excitatory pathways in the enteric nervous system in addition to the known vagal pathways.
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Comparative Study
Nicotine physical dependence in the mouse: involvement of the alpha7 nicotinic receptor subtype.
Although chronic nicotine produces dependence in mice, the role of specific nicotinic receptors has not been examined in knockout animals. The present study utilized alpha7 nicotinic receptor knockout mice to explore the role of this receptor subunit in nicotine dependence. ⋯ Nicotine withdrawal produced increased somatic signs in both strains and hyperalgesia in wild-type, but not in knockout animals. These results indicate that the alpha7 nicotinic receptor subunit may mediate some aspects of nicotine dependence.
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Comparative Study
The role of substance P and bradykinin in the cough reflex and bronchoconstriction in guinea-pigs.
In this study we investigated the ability of aerosolized substance P to induce either cough or bronchoconstriction in guinea-pigs. We have also examined whether pre-treatment, by the inhaled route, of animals with a combination of the neutral endopeptidase inhibitor, phosphoramidon (10(-3) M), and the diaminopeptidase IV inhibitor, diprotin A (10(-3) M), enhances the airway response to substance P. Moreover, we also assessed whether aerosol pre-treatment of guinea-pigs with either substance P or bradykinin, at 10(-4) M, affects the citric acid-induced cough and/or bronchoconstriction. ⋯ In contrast, exposure of guinea-pigs to bradykinin (10(-4) M) prior to the citric acid challenge resulted in a significant enhancement of the cough response (9.2+/-1.9 vs. 25.8+/-2.5; P<0.05) but not the bronchoconstriction (P>0.05). These data do not support a major peripheral role for substance P in the cough reflex, although bradykinin is able to sensitize the cough reflex. Furthermore, these data suggest that bronchoconstriction, induced by citric acid, is not responsible for the cough associated with this irritant.