Abstract
1 The time courses of the pre- and post-junctional effects of clonidine were examined on heart rate and blood pressure and on the isometric tension responses of the vas deferens and anococcygeus in situ in the pithed rat. Plasma levels of clonidine were also monitored. 2 The time courses of the pre-junctional inhibition of sympathetic nerve mediated responses in all tissues monitored were related to the plasma levels of clonidine, but the degree of inhibition which was observed varied with the tissue and with the test stimulus employed. 3 The post-junctional agonist effects of clonidine, expecially at low doses, exhibited an initial 'peak' followed by a decline to a lower plateau. This decline of the response was not due to receptor desensitization but was related to a decline in the plasma clonidine level from an initially high value caused by injection of a bolus. 4 The factors determining the time course of drugs' effects in the preparation are discussed and it is concluded that pre- and post-junctional responses should be compared at a point in time after injection of the-drug, at which equilibration has occurred.
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- Armstrong J. M., Boura A. L. Effects of clonidine and guanethidine on peripheral sympathetic nerve function in the pithed rat. Br J Pharmacol. 1973 Apr;47(4):850–852. doi: 10.1111/j.1476-5381.1973.tb08214.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown C. M., McGrath J. C., Summers R. J. The effects of alpha-adrenoceptor agonists and antagonists on responses of transmurally stimulated prostatic and epididymal portions of the isolated vas deferens of the rat. Br J Pharmacol. 1979 Aug;66(4):553–564. doi: 10.1111/j.1476-5381.1979.tb13694.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cavero I., Gomeni R., Lefèure F., Roach A. G. Time-course analysis of the cardiovascular effects of clonidine resulting from the activation of cardiac pre- and vascular postsynaptic alpha-adrenoceptors in the pithed rat [proceedings]. Br J Pharmacol. 1978 Mar;62(3):468P–468P. [PMC free article] [PubMed] [Google Scholar]
- Clanachan A. S., McGrath J. C. Effects of ketamine on the peripheral autonomic nervous system of the rat. Br J Pharmacol. 1976 Oct;58(2):247–252. doi: 10.1111/j.1476-5381.1976.tb10402.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Docherty J. R., McGrath J. C. An analysis of some factors influencing alpha-adrenoceptor feed-back at the sympathetic junction in the rat heart. Br J Pharmacol. 1979 May;66(1):55–63. doi: 10.1111/j.1476-5381.1979.tb16097.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Docherty J. R., McGrath J. C. Effect of pre-synaptic alpha-adrenoceptor blockade on the chronotropic response to cardiac sympathetic nerve stimulation in the pithed rat [proceedings]. J Physiol. 1977 Dec;273(2):63P–64P. [PubMed] [Google Scholar]
- Docherty J. R., McGrath J. C. Potentiation of cardiac sympathetic nerve responses in vivo by pancuronium bromide [proceedings]. Br J Pharmacol. 1977 Nov;61(3):472P–473P. [PMC free article] [PubMed] [Google Scholar]
- Docherty J. R., McGrath J. C. Sympathomimetic effects of pancuronium bromide on the cardiovascular system of the pithed rat: a comparison with the effects of drugs blocking the neuronal uptake of noradrenaline. Br J Pharmacol. 1978 Dec;64(4):589–599. doi: 10.1111/j.1476-5381.1978.tb17321.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Docherty J. R., McGrath J. C. Time course of the pre- and post-junctional effects of clonidine in the pithed rat [proceedings]. Br J Pharmacol. 1978 Nov;64(3):419P–420P. [PMC free article] [PubMed] [Google Scholar]
- Doxey J. C., Everitt J. Inhibitory effects of clonidine on responses to sympathetic nerve stimulation in the pithed rat. Br J Pharmacol. 1977 Dec;61(4):559–566. doi: 10.1111/j.1476-5381.1977.tb07548.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Drew G. M. Effects of alpha-adrenoceptor agonists and antagonists on pre- and postsynaptically located alpha-adrenoceptors. Eur J Pharmacol. 1976 Apr;36(2):313–320. doi: 10.1016/0014-2999(76)90084-4. [DOI] [PubMed] [Google Scholar]
- Drew G. M. Pharmacological characterisation of the presynaptic alpha-adrenoceptor in the rat vas deferens. Eur J Pharmacol. 1977 Mar 21;42(2):123–130. doi: 10.1016/0014-2999(77)90351-x. [DOI] [PubMed] [Google Scholar]
- Frisk-Holmberg M., Edlund P. O., Paalzow L. Pharmacokinetics of clonidine and its relation to the hypotensive effect in patients. Br J Clin Pharmacol. 1978 Sep;6(3):227–232. doi: 10.1111/j.1365-2125.1978.tb04589.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillespie J. S., Maclaren A., Pollock D. A method of stimulating different segments of the autonomic outflow from the spinal column to various organs in the pithed cat and rat. Br J Pharmacol. 1970 Oct;40(2):257–267. doi: 10.1111/j.1476-5381.1970.tb09919.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillespie J. S., McGrath J. C. The effect of pithing and of nerve stimulation on the depletion of noradrenaline by reserpine in the rat anococcygeus muscle and vas deferens. Br J Pharmacol. 1974 Dec;52(4):585–590. doi: 10.1111/j.1476-5381.1974.tb09727.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillespie J. S., McGrath J. C. The spinal origin of the motor and inhibitory innervation of the rat anococcygeus muscles. J Physiol. 1973 May;230(3):659–672. doi: 10.1113/jphysiol.1973.sp010210. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillespie J. S. The rat anococcygeus muscle and its response to nerve stimulation and to some drugs. Br J Pharmacol. 1972 Jul;45(3):404–416. doi: 10.1111/j.1476-5381.1972.tb08097.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Idowu O. A., Zar M. A. Inhibitory effect of clonidine on a peripheral adrenergic synapse [proceedings]. Br J Pharmacol. 1976 Oct;58(2):278P–278P. [PMC free article] [PubMed] [Google Scholar]
- McGrath J. C. Adrenergic and 'non-adrenergic' components in the contractile response of the vas deferens to a single indirect stimulus. J Physiol. 1978 Oct;283:23–39. doi: 10.1113/jphysiol.1978.sp012486. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sjöstrand N. O., Swedin G. On the mechanism of the enhancement by smooth muscle stimulants of the motor responses of the guinea-pig vas deferens to nerve stimulation. Acta Physiol Scand. 1974 Mar;90(3):513–521. doi: 10.1111/j.1748-1716.1974.tb05616.x. [DOI] [PubMed] [Google Scholar]
- Starke K., Montel H., Gayk W., Merker R. Comparison of the effects of clonidine on pre- and postsynaptic adrenoceptors in the rabbit pulmonary artery. Alpha-sympathomimetic inhibition of Neurogenic vasoconstriction. Naunyn Schmiedebergs Arch Pharmacol. 1974;285(2):133–150. doi: 10.1007/BF00501149. [DOI] [PubMed] [Google Scholar]