2001 Fiscal Year Final Research Report Summary
Prolongation of nerve block by complexation of local anesthetic with cyclodextrin
| Project/Area Number |
12470323
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Anesthesiology/Resuscitation studies
|
|---|
| Research Institution | Miyazaki Medical Collage |
|---|
Principal Investigator |
TAKASAKI Mayumi Miyazaki Medical College, Department of Anesthesiology, Professor, 医学部, 教授 (30094212)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TANIGUCHI Masahiko Miyazaki Medical College, Department of Anesthesiology, Instructor, 医学部, 助手 (70305085)
NAKAMURA Tadashi Miyazaki Medical College, Department of Anesthesiology, Instructor, 医学部, 助手 (60217859)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Keywords | levobupivacaine / cyclodextrin / prolongation / local anesthetic |
|---|
| Research Abstract |
Background : Neural blockade is widely used for acute and chronic pain management, however existing local anesthetics have a short duration of action. The cyclodextrin-based drug delivery system, consisting of levobupivacaine complexed with maltosyl-β-cyclodextrin, was used in spinal and sciatic nerve blocks in rats, anticipating the prolonged local anesthetic effect.
Methods : Muscle tone and tail flick latency were studied over time following intrathecal administration of the complex of levobupivacaine with maltosyl-β-cyclodextrin in rats. In addition, the time course of changes in proprioception, motor function, and nociception following circumferential subcutaneous administration of the complex to the sciatic nerve were also examined.
Results : With the intrathecal block, all rats stopped tail movement immediately after injection of the local anesthetics. Intrathecal injection of the complexed levobupivacaine significantly prolonged motor blockade, but not sensory blockade. In sciatic nerve block, all rats were temporarily immobilized after injection of levobupivacaine, its complexed form significantly prolonging the anesthetic effects, as evaluated by proprioception, motor function, and nociception. Furthermore, neither histological nor neurological signs were observed following the nerve blocks with the levobupivacaine preparations tested.
Conclusions : The complexation of levobupivacaine with maltosyl-β-cyclodextrin safely prolonged the anesthetic effect of levobupivacaine in both intrathecal and sciatic nerve blocks in rats. The complexation of levobupivacaine with maltosyl-β-cyclodextrin is particularly useful for designing safer and long-acting formulations for levobupivacaine in both intrathecal and sciatic nerve blocks.
|
