An analysis of the effects of clonidine and three structural isomers on transmission in rat superior cervical ganglia in vitro.
alpha-Adrenoceptors mediating inhibition of release of acetylcholine in the superior cervical ganglia of the rat have previously been characterized as of the alpha 2-subtype (Brown and Caulfield, 1981). In the present study, the effects of clonidine (2,6-dichlorophenylimino-2-imidazolidine), the 2,3- 2,4- and 2,5-dichloro isomers (St 476, St 363 and St 475) and the 3,4-dihydroxy analogue (DPI) were examined on transmission in this tissue. Compound action potentials (CAP; supramaximal preganglionic stimulation at 0.2 Hz) were recorded extracellularly. Clonidine, DPI and adrenaline inhibited the compound action potential; concentration-response curves were shifted to the right by phentolamine. The maximum inhibition of the compound action potential was similar for epinephrine and DPI. However, for clonidine a secondary inhibitory component, leading to almost complete blockade of the compound action potential, was seen in concentrations greater than 10 microM; similar effects were seen for the lipid-soluble analogues St 476, St 363 and St 475, suggesting a non-specific effect. In smaller concentrations, St 476, St 363 and St 475 exerted only weak inhibition of the CAP; St 363 and St 475 actually increased the height of the compound action potential, in a similar manner to phentolamine (0.1-3 microM), and all three analogues blocked the inhibitory effects of adrenaline. These latter data suggest partial agonist actions for St 476, St 363 and St 475. The rank order of inhibitory effectiveness (clonidine greater than St 476 greater than St 363 greater than St 475) parallels that for acute hypotensive effects in rats (Timmermans and van Zwieten, 1977a). The results suggest that sympatho-inhibitory effects of some imidazolidines may not result solely from activation of presynaptic alpha 2-adrenoceptors.
Medgett
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D003864:Depression, Chemical; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005728:Ganglia, Sympathetic / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007536:Isomerism; D008297:Male; D009433:Neural Inhibition; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects*
D003000:Clonidine; D004837:Epinephrine