らい性末梢神経炎治療の可能性を目途とした酸性消炎剤の麻酔作用を発現する誘導体の研究

儀同 政一; 堤 貞衛

doi:10.5025/hansen1977.52.156

Studies on the Derivatives Showing Local Anesthetic Actions of Several Acidic Antiinflammatory Drugs, Aiming at the Possibility of Treatment for Leprous Neuritis

MASAICHI GIDOH, SADAE TSUTSUMI

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JOURNAL FREE ACCESS

1983 Volume 52 Issue 3 Pages 156-164

DOI https://doi.org/10.5025/hansen1977.52.156

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Published: September 30, 1983 Received: November 18, 1982 Available on J-STAGE: February 26, 2008 Accepted: - Advance online publication: - Revised: -
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Date of correction: February 26, 2008 Reason for correction: - Correction: DTRECEIVED Details: Right : 19821118

Date of correction: February 26, 2008 Reason for correction: - Correction: ABSTRACT Details: Right : 1. Diethylaminoethylesters (DEAF) of Brufen (BF) and Mefenamic acid (MA) were synthesized together with diethylaminoethylamides (DEAEAM) of BF and Carprofen (CPF).
2. Their local anesthetic effects were examined by blink and skin reflux tests. All of them showed notable effects. Especially, BF-DEAE and BF-DEAEAM exhibited the surface local anesthetic effects 20 fold and 10 fold stronger than that of Procaine•Hcl, respectively. CPF-DEAEAM also exhibited the infiltration local anesthetic effect twice stronger than that of Xylocaine•HCl.
3. However, several problems remained. BF-DEAE hydrolyzed very rapidly in a heparinized rat plasma. Its acute toxicity was 10 fold higher than that of BF when intraveneously dosed to mice whereas it was comparable to that of BF when dosed orally. Both of BF-DEAE and CPF-DEAEAM, especially the latter caused the corneal clouding in the high concentrations, which may be due to its surfactant activity.
4. BF-DEAEAM was stable in the rat plasma and its LD₅₀ value nearly reached to 1250mg/kg by mice.
5. Standing on the contradiction between the eradication of leprosy bacilli inside peripheral nerves and the resultant possible undesirable host reactions in the nerves, the necessity to discover a drug remissive the inflammation in the peripheral nerves through its local use was discussed.

Date of correction: February 26, 2008 Reason for correction: - Correction: AUTHOR Details: [in Japanese]

Date of correction: February 26, 2008 Reason for correction: - Correction: PDF FILE Details: -

Date of correction: February 26, 2008 Reason for correction: - Correction: PDF FILE Details: -

Abstract

1. Diethylaminoethylesters (DEAF) of Brufen (BF) and Mefenamic acid (MA) were synthesized together with diethylaminoethylamides (DEAEAM) of BF and Carprofen (CPF).
2. Their local anesthetic effects were examined by blink and skin reflux tests. All of them showed notable effects. Especially, BF-DEAE and BF-DEAEAM exhibited the surface local anesthetic effects 20 fold and 10 fold stronger than that of Procaine•Hcl, respectively. CPF-DEAEAM also exhibited the infiltration local anesthetic effect twice stronger than that of Xylocaine•HCl.
3. However, several problems remained. BF-DEAE hydrolyzed very rapidly in a heparinized rat plasma. Its acute toxicity was 10 fold higher than that of BF when intraveneously dosed to mice whereas it was comparable to that of BF when dosed orally. Both of BF-DEAE and CPF-DEAEAM, especially the latter caused the corneal clouding in the high concentrations, which may be due to its surfactant activity.
4. BF-DEAEAM was stable in the rat plasma and its LD₅₀ value nearly reached to 1250mg/kg by mice.
5. Standing on the contradiction between the eradication of leprosy bacilli inside peripheral nerves and the resultant possible undesirable host reactions in the nerves, the necessity to discover a drug remissive the inflammation in the peripheral nerves through its local use was discussed.

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