In vitro methods for the assessment of the inhibitory effects of antidepressants in rat parotid glands.
The present study evaluates suitable in vitro methods for the assessment of the inhibiting properties of four principally different antidepressant drugs. This was done by comparing the acute effects of antidepressants on autonomic receptor binding (homogenates) together with parallel tests evaluating the biological activities of the receptor systems in collagenase-isolated rat parotid acini. The responses were measured as receptor-activated changes in cyclic nucleotide formation and acinar oxygen consumption. Muscarinic acetylcholine receptor binding, carbachol-induced cGMP formation, and oxygen consumption all reflected the various inhibiting effects of the antidepressants tested. Measurements of the carbachol-induced O2 consumption was however, the most sensitive method and may be considered a well-suited and reliable parameter concerning the expected severity of anticholinergic side-effects caused by medication. The disturbing 'dry mouth' symptoms following treatment with amitriptyline or mianserin are however, also attributed to their substantial adrenoceptor-blocking effects, which are best demonstrated by alpha 1-adrenoceptor binding studies in combination with measurements of the adrenaline-induced O2 consumption in the rat parotid gland.
Glenert
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Department of Pathology and Medicine, Royal Dental College, Panum Institute, Copenhagen, Denmark.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D010306:Parotid Gland / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*
D000928:Antidepressive Agents; D008024:Ligands; D011941:Receptors, Adrenergic; D011976:Receptors, Muscarinic; D002217:Carbachol; D000242:Cyclic AMP; D006152:Cyclic GMP