Abstract
The selective muscarinic antagonists procyclidine, pirenzepine, 4-DAMP, pFHHSiD, and ADFX-116, were used through eye-drops delivery, to induce pupillary mydriasis in rats. The relative mydriatic potencies of these antagonists were found to correlate with their relative known pharmacological affinities towards the M3 subtype of muscarinic receptors. These results suggest that miosis and mydriasis induced through the activation or blockade of muscarinic receptors in the iris are exerted through M3 muscarinic receptors. Chronic lithium treatment, reaching therapeutic blood levels had no effect on the ability of the various muscarinic antagonists to induce mydriasis. Lithium was recently demonstrated to inhibit the coupling of both muscarinic-cholinergic and β-adrenergic receptors to G proteins, suggesting alteration of the function of G proteins by lithium, as the single site for both the antimanic and the antidepressant effects of this drug. It was found that lithium-sensitive muscarinic agonist effects on G protein function are directed through M1 muscarinic receptors. Lithium had no effect on the function of G protein coupled to M2 muscarinic receptors. Our present findings of null effects of lithium on M3 mediated pupillary responses to muscarinic antagonists may help to further the differentiation of lithium effects on muscarinic receptor coupled mechanisms. Only the M1 receptor functions are selectively inhibited by lithium, while signal transduction beyond M2 and M3 muscarnic receptors are unaffected by this ion.
Original language | English |
---|---|
Pages (from-to) | 279-283 |
Number of pages | 5 |
Journal | Lithium |
Volume | 4 |
Issue number | 4 |
State | Published - 1 Jan 1993 |
ASJC Scopus subject areas
- Pharmacology (medical)