Biomedical subjects

K Imano

Publications and source records attributed to K Imano.

12 recordsLinked to original sources

PubMed1997

Antinociceptive and antidepressant-like profiles of BL-2401, a novel enkephalinase inhibitor, in mice and rats.

To clarify the properties of BL-2401 ((+/-)-3-[2-benzyl-3-(propionylthio) propionyl]amino-5-methylbenzoic acid), a novel enkephalinase inhibitor, we examined its antinociceptive and antidepressant-like activities after oral administration, along with their association with endogenous opioid systems. BL-2401 produced an antinociceptive effect after oral administration in the mouse phenylbenzoquinone writhing test (ED50: 12.4 mg/kg) and the rat acetic acid writhing test (ED50: 55.8 mg/kg), the antinociceptive effect being antagonized by naloxone hydrochloride. BL-2401 also relieved arthritis-induced hyperalgesia in rats. In the mouse hot-plate and tail pressure tests, BL-2401 showed significant but modest antinociception at higher doses (200 and 400 mg/kg). In addition, BL-2401 (100 mg/kg) produced a naloxone-reversible antidepressant-like effect in the mouse forced swimming test. As for the mechanism of the action, the active metabolite of BL-2401, BL-2240 ((+/-)-3-(2-benzyl-3-mercaptopropionyl) amino-5-methylbenzoic acid), selectively inhibited enkephalinase in vitro (IC50: 5.2 nM). Oral administration of BL-2401 to mice significantly inhibited the enkephalinase activity in the striatum and also potentiated the antinociceptive effect of (D-Ala2,Met5)-enkephalin given intracisternally. These findings indicate that BL-2401 is an orally active enkephalinase inhibitor and may produce antinociceptive and antidepressant-like effects in association with endogenous opioid systems.

Administration, Oral↗

PubMed1994

[Pharmacological study of ebastine, a novel histamine H1-receptor antagonist].

The anti-allergic activity of ebastine, a novel antihistamine, was assessed in comparison with several antihistamines. 1) Orally administered ebastine dose-dependently inhibited 7-day homologous passive cutaneous anaphylaxis (PCA), experimental allergic rhinitis and experimental asthma in guinea pigs or rats (ED50-values were 2.17, 0.29 and 0.35 mg/kg, respectively); and its anti-allergic activity was more potent than those of terfenadine and mequitazine. Moreover, its PCA-inhibitory activity was still observed 24 hr after the administration. 2) Orally administered ebastine also inhibited histamine-induced skin reaction in rats (ED50: 1.10 mg/kg). 3) In isolated guinea pig trachea, ebastine had no effect on histamine-induced contraction, but carebastine, a main metabolite of ebastine, inhibited this contraction (IC50: 0.12 microM). 4) Carebastine (30-100 microM) suppressed the histamine release from rat peritoneal mast cells and human basophils. 5) Ebastine at a high oral dose showed slight inhibition of the specific binding of 3H-mepyramine to the histamine H1-receptor in rat brain. This binding-inhibitory activity of ebastine was little more potent than that of terfenadine, but much less potent than those of mequitazine and ketotifen. These results indicated that ebastine has potent and long acting anti-allergic activity with few side effects based on the antihistaminic activity in the central nervous system. Furthermore, it was suggested that these effects of ebastine are due to the action of a main metabolite, carebastine.

Administration, Oral↗

PubMed1993

Involvement of corticotropin-releasing factor in the antinociception produced by interleukin-1 in mice.

Recombinant human interleukin-1 alpha (rHu-IL-1 alpha) has been indicated to produce central antinociception in the mouse phenylquinone writhing test, the antinociception being unaffected by naloxone. Because interleukin-1 has been demonstrated to be a potent releaser of corticotropin-releasing factor (CRF) from the hypothalamus, we were interested to see whether CRF is involved in the antinociception induced by rHu-IL-1 alpha. In the present study, we examined this question using the mouse phenylquinone writhing test, in which mice were injected with various doses of CRF and/or alpha-helical CRF-(9-41), a CRF antagonist. CRF inhibited writhing responses after i.v. and intracisternal (i.c.) administration. The antinociception elicited by i.v. administered CRF was antagonized by i.v. injection, but not by i.c. injection, of alpha-helical CRF-(9-41). The antinociception elicited by i.e. administered CRF was antagonized by i.c. injection of alpha-helical CRF-(9-41) and s.c. treatment of opioid antagonists. rHu-IL-1 alpha-induced antinociception was attenuated by i.v. injection, but not by i.c. injection, of alpha-helical CRF-(9-41). These findings suggest that CRF possesses antinociceptive efficacy by both peripheral and central mechanisms, and that the antinociception induced by rHu-IL-1 alpha is mediated, at least in part, by the peripheral action of CRF.

Animals↗

PubMed1993

Inhibition of passive sensitization of human peripheral basophils by synthetic human immunoglobulin E peptide fragments.

To delineate the binding site in the human immunoglobulin E (IgE) molecule to the Fc epsilon receptor on basophils and mast cells, we chemically synthesized a total of 71 peptide fragments within the sequence Ser300-Lys547 in the human IgE molecule. The synthetic peptides were tested for their capacity to inhibit passive sensitization of human peripheral basophils with atopic patient's serum containing the specific IgE against dust mites in vitro. It was found that a peptide fragment, Pro345-Ile356, potently inhibited the passive sensitization. To clarify the minimal active core, various analogues, such as shortened, substituted (by Gly or Ala residue), omission and retro-sequence peptides, were synthesized and assayed. The results suggested that the sequence Pro345-Lys352 in the human IgE molecule would be an IgE binding site, and that a synthetic octapeptide, Pro345-Phe-Asp-Leu-Phe-Ile-Arg-Lys352, inhibited the passive sensitization, probably by occupying the Fc epsilon receptor sites on the cells.

Allergens↗

PubMed1981