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Curr Med Chem. 2009;16(11):1366-71.

Recovery of locomotor function with combinatory drug treatments designed to synergistically activate specific neuronal networks.

Author information

1
Laval University Medical Center (CHUL - CHUQ), Neuroscience Unit, RC-9800, 2705 Laurier Blvd, Quebec City, Quebec, G1V 4G2, Canada. Pierre.Guertin@crchul.ulaval.ca

Abstract

Spinal cord injury (SCI) is a devastating condition generally leading to a permanent and irreversible loss of sensory and motor functions. We have identified recently a number of serotonergic, adrenergic and dopaminergic receptor agonists or precursors that can acutely elicit some motor and locomotor-like movements in completely spinal cord-transected (thoracic level) animals. However, only partial central network-activating effects were found with single molecules since none administered separately could elicit weight-bearing and functional stepping movements in Tx animals. In turn, a recent breakthrough revealed that full spinal locomotor network-activating effects may be induced with synergistic drug combinations. Indeed, specific cocktails comprising some of these agonists and precursors were found, indeed, to powerfully generate weight-bearing stepping with plantar foot placement in untrained, non-assisted and non-sensory-stimulated Tx mice. This significant finding provides clear evidence suggesting that combinatorial approaches based on drug-drug synergistic interactions may constitute innovative solutions for the design and development of novel pharmacological therapies in the field of SCI and related neurological disorders.

PMID:
19355892
[Indexed for MEDLINE]

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