Serotonergic manipulations in experimental neoplastic spinal cord compression

Journal of Neurosurgery
T Z Siegal, T Siegal


The effects of differing strategies of serotonergic manipulation on vascular permeability, prostaglandin E2 (PGE2) synthesis, and the clinical course are evaluated in an experimental model of neoplastic spinal cord compression in rats. Serotonergic manipulations include in vivo inhibition of serotonin (5-HT) synthesis by p-chlorophenylalanine (p-CPA) and in vivo blockage of serotonin type 2 (5-HT2) receptors either by the selective antagonist ketanserin or by cyproheptadine. In paralyzed rats, the ratio of 5-hydroxyindole-3-acetic acid (5-HIAA) to 5-HT is significantly elevated in the compressed segments, suggesting that 5-HT utilization is increased. Treatment with p-CPA attenuates spinal 5-HT levels by 62.8% +/- 5.1% (mean +/- standard deviation) and reduces the elevated 5-HIAA:5-HT ratio to the normal value. The increased synthesis of PGE2 observed in the compressed cord is unaffected by p-CPA or ketanserin treatment but is markedly attenuated by cyproheptadine. Ketanserin reduces the 10-fold increase in spinal cord permeability observed in paralyzed rats in a clearly dose-related manner. If given at the first sign of neurological dysfunction, ketanserin delays the onset of paraplegia with the 1-mg/kg dose being clearly supe...Continue Reading


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Related Concepts

Vascular Permeability
Dose-Response Relationship, Drug
Hydroxyindoleacetic Acid
Fenclonine, (D)-Isomer
Rats, Inbred F344
Serotonin Antagonists

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