Natural GABA agonists

The enhanced 5-HT release would probably act via the activation of postsynaptic 5-HT2 receptors that remain normosensitive after the 8-week SSRI treatment (el Mansari and Blier, 1997). Indeed, the response of orbitofrontal cortex neurons to 5-HT and 5-HT2 agonists is unaltered, whereas that to a 5-HTia agonist is decreased after such treatment. It has not been conclusively shown that these 5-HT2 receptors are located directly on the glutamatergic pyramidal neurons or on inhibitory GABA interneurons. Wherever their precise localization, the effect of 5-HT on these neurons, which send an excitatory output to the caudate nucleus, is inhibitory in nature, which could account for the dampening of the hyperactivity observed following successful SSRI treatment. These results clearly identify the terminal 5-HTib autoreceptor and the postsynaptic 5-HT2 receptors as potential novel targets for the treatment of OCD. 

In other instances such apparent hybrid activities could be missing or less prominent, as shows the example of epibatidine, a powerful alkaloid from the skin of several arrow poison frogs. Synthetic (+)- and natural (-)-epibatidine have potent agonist activity at ganglionic-type nicotinic receptors. The epibatidines have little or no activity at a variety of other central receptors, including opioid receptors, muscarinic receptors, adrenergic receptors, dopamine receptors, serotonin receptors, and GABA receptors [81]. 

The furanocoumarin compound phellopterin was shown to be a partial agonist of the central benzodiazepine receptors. Two other naturally occurring furanocoumarins, byakangelicol and imperatorin, exhibited significantly less potent binding activity to the benzodiazepine site of the rat brain GABA-A receptor (Dekermendjian et al. 1996). 

Brady, K., Herrera, Y. and Zenick, H. (1975). Influence of parental lead exposure on subsequent learning ability of offspring. Pharmacol. Biochem. Behav., 3, 561 Brashear, C. W., Kopp, V. J. and Krigman, M. R. (1978). Effect of lead on the developing peripheral nervous system. J. Neuropathy Exp. Neurol., 31 414 Brennan, M. J. W. and Cantrill, R. C. (1979). o-Aminolaevulinic acid is a potent agonist for GABA autoreceptors. Nature (London), 280, 514 Brown, D. R. Neonatal lead exposure in the rat decreased learning as a function of age and blood lead concentrations. Toxicol. Appl. Pharmacol., 32, 628 Bull, R. J., Lutkenhoff, S. D., McCarty, G. E. and Miller, R. G. (1979). Delays in the postnatal increase of cerebral cytochrome concentrations in lead-exposed rats. Neuropharmacol, 18, 83... 

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