Effects of an alpha‐2 adrenoceptor antagonist, Org 3770, upon the autonomic function of the pupil

Abstract

The effects of a single oral dose of an alpha-2 adrenoceptor antagonist, Org 3770 (30mg), upon the autonomic function of the human pupil have been investigated in six volunteers. Org 3770 reduced pupil diameter, possibly as a result of its alpha-2 adrenoceptor blocking activity. Org 3770 did not reduce the mydriatric effect of phenylephrine and tyramine, nor was the miotic response to pilocarpine affected. These results are consistent with a blockade by Org 3770 of central alpha-2 adrenoceptors.

Potential Antidepressants Displayed Combined α2-Adrenoceptor Antagonist and Monoamine Uptake Inhibitor Properties

“…These presynaptic receptors also slowly desensitize leading to a gradual increase of therapeutically effective monoamine concentration in the presence of antidepressant agents. This hypothesis may be tested either by coadministration of a TCA, a SSRI, or a SNRI with an antagonist of these auto- or heteroreceptors or by administration of a drug endowed with both properties. − …”

“…This hypothesis may be tested either by coadministration of a TCA, a SSRI, or a SNRI with an antagonist of these auto-or heteroreceptors or by administration of a drug endowed with both properties. [5][6][7][8][9][10] A second strategy implying the discovery of molecules acting both as NA 11,12 and/or SER 13 uptake inhibitors and as antagonists at presynaptic auto-or heteroreceptors has been little exploited. Our research effort aimed to identify a molecule endowed with NA and/or SER uptake inhibitor properties and antagonist activity at presynaptic R 2 -adrenergic autoreceptors.…”

“…This change permitted a differentiation of the two nitrogen atoms and revealed their potential ability to afford contrasting pharmacological profiles. In addition, we have evaluated the importance of the imidazole nucleus by replacing it with different heterocycles (5)(6)(7)(8), examined the importance of the dihydronaphthalene skeleton by undertaking diverse modifications (9)(10)(11)(12)(13)(14)(15), and, finally, rigidified the molecule (16)(17)(18)(19)(20)(21)(22)(23)(24) in order to define the active conformation required for pharmacological efficacy.…”