Neuropharmacological studies of biogenic amine receptors on invertebrate and mammalian central neurones

Batta, Scarlett (1978) Neuropharmacological studies of biogenic amine receptors on invertebrate and mammalian central neurones. University of Southampton, Doctoral Thesis.

Abstract

In the experiments described in this thesis, drug receptor interactions were studied using an invertebrate model system. The three classes of biogenic amines and their antagonists examined were dopamine, octopamins and phenylethanolamine. Most attention has been focused on the structural requirements for dopamine induced inhibition or excitation on identified neurones in the brain of the snail Helix aspersa. Through the use of cyclic rigid analogues of dopamine, evidence Is presented suggesting that both types of receptor have the same conformational requirements for dopamine and that the active conformation of dopamine at its receptor site is the extended form (6-rotamer). Thus the (+)-enantiomer of 2-amino-,6,7-dihydroxyl-1,2, 3,4-tetrahydronapthalene (+)ADTN is the. most potent dopamine agonist yet developed. The results in this study show the similarity between the dopamine receptor mediating neuronal activity in invertebrates and those involved in stimulating cyclic AMP production in the rat striatum and nucleus accumbens. The neuroleptics, classical dopamine antagonists, were tested on both types of response. Results indicate a poor correlation between clinical efficacy and dopamine antagonism in the invertebrate system. Consequently the snail brain would not be a useful screen for neuroleptics.Experiments were performed to show the existence of a separate octopamine receptor differing from the dopamine receptor. Using a variety of phenylethylamine derivatives we were able to show the structural requirements for octopamine like activity include a hydroxyl group at the three or four position of the benzene ring and on the (-carbon atom of the ethylamine side chain. The action of octopamine was antagonised by phentolamine, however, this effect was not specific. Evidence has been presented for the presence of a seperate phenylethanolamine receptor in the snail brain. An inhibitory response to iontophoretically applied phenylethanolamine was observed in Purkinje cells of the rat cerebellum. Our results Imply that the response to phenylethanolamine is not mediated through and activation of noradrenergic receptors.

This record has no associated files available for download.

Contributors

Download statistics