Cutaneous analgesia after subcutaneous injection of memantine and amantadine and their systemic toxicity in rats

Yu Wen Chen, Ja Ping Shieh, Yu Chung Chen, Yuk Man Leung, Ching-Hsia Hung, Jhi Joung Wang

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The purpose of the study is to find subcutaneous equianalgesic doses of memantine, amantadine and bupivacaine and use these doses to quantify the cardiovascular and central nervous system toxicity of these agents after intravenous administration. Memantine, amantadine and bupivacaine, a local anesthetic, in a dose-related fashion were determined for cutaneous analgesia by a block of the cutaneous trunci muscle reflex in rats, and equipotent doses were calculated. Following rapid intravenous infusion of equianalgesic bupivacaine, memantine, amantadine and saline (vehicle) in rats, we observed the onset time of seizure, apnea and impending death, and monitored mean arterial blood pressure and heart rate. Memantine and amantadine elicited dose-dependent cutaneous analgesia. At the 50 effective dose (ED50), the rank of potencies was bupivacaine [1.8 (1.7-2.0)]>memantine [19.1 (17.6-21.8)]>amantadine [36.1 (32.0-40.3)] (P<0.05). On ED25, ED50 and ED75 basis, the duration caused by bupivacaine was similar to that caused by memantine or amantadine. At equianalgesic doses, the infusion time of memantine or amantadine required to induce seizure, impending death, and apnea was longer than that of bupivacaine during rapid intravenous infusion (P<0.01). The decreasing slope in mean arterial blood pressure and heart rate was slower with memantine and amantadine when compared with bupivacaine at equivalent doses (P<0.01). Our data showed that memantine and amantadine (i) were equal to bupivacaine at producing durations of cutaneous analgesia but (ii) were less likely than bupivacaine to cause cardiovascular and central nervous system toxicity.

Original languageEnglish
Pages (from-to)25-30
Number of pages6
JournalEuropean Journal of Pharmacology
Volume693
Issue number1-3
DOIs
Publication statusPublished - 2012 Oct 15

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Memantine
Amantadine
Bupivacaine
Subcutaneous Injections
Analgesia
Skin
Arterial Pressure
Apnea
Intravenous Infusions
Seizures
Heart Rate
Central Nervous System Agents
Local Anesthetics
Intravenous Administration
Reflex
Central Nervous System
Muscles

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Chen, Yu Wen ; Shieh, Ja Ping ; Chen, Yu Chung ; Leung, Yuk Man ; Hung, Ching-Hsia ; Wang, Jhi Joung. / Cutaneous analgesia after subcutaneous injection of memantine and amantadine and their systemic toxicity in rats. In: European Journal of Pharmacology. 2012 ; Vol. 693, No. 1-3. pp. 25-30.
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Cutaneous analgesia after subcutaneous injection of memantine and amantadine and their systemic toxicity in rats. / Chen, Yu Wen; Shieh, Ja Ping; Chen, Yu Chung; Leung, Yuk Man; Hung, Ching-Hsia; Wang, Jhi Joung.

In: European Journal of Pharmacology, Vol. 693, No. 1-3, 15.10.2012, p. 25-30.

Research output: Contribution to journalArticle

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