Pre-synaptic autoreceptors

The dopamine-containing nigro-neostriatal dopaminergic neurons possess receptors for dopamine. These dopamine receptors occur on both the nerve terminals within the neostriatum (pre-synaptic autoreceptors) as well as on the soma and dendrites (soma-dendritic autoreceptors). Stimulation of either category of autoreceptor can regulate the synthesis, turnover and release of dopamine in the neostriatum but by different mechanisms. 

Clonidine (Catapres) is an imidazoline which is an agonist to ctj-adrenoceptors (postsynaptic) in the brain, stimulation of which suppresses S5unpathetic outflow and reduces blood pressure. At high doses it also activates peripheral a -adrenoceptors (pre-synaptic autoreceptors) on the adrenergic nerve ending these mediate negative feedback suppression of noradrenaline release. In overdose clonidine can stimulate peripheral Oj-adrenoceptors (postsynaptic) and thus cause hypertension by vasoconstriction. Clonidine was discovered to be hypotensive, not by the pharmacologists who tested it in the laboratory but by a physician who used it on himself as nose drops for a common cold. The tl is 6 h. 

S. O. Thorberg, S. Berg, J. Lundstrom, B. Pettersson, A. Wijkstrom, D. Sanchez, P. Lind-berg, J. L. G. Nilsson, Carbamate Ester Derivatives as Potential Prodrugs of the Pre-synaptic Dopamine Autoreceptor Agonist (-)-3-(3-Hydroxyphenyl)-A-propylpiperidine J. Med. Chem. 1987, 30, 2008-2012. 

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