Transcript
Now, many of you understand the pharmacology of salivary glands and know that there are a number of muscarinic receptor subtypes which are expressed there. But what we understand is that more likely than not the problem related to clozapine has to do with its metabolite norclozapine which is also called N-desmethylclozapine. This turns out to be a muscarinic M1 agonist and we believe this is responsible for the drooling. So although the parent compound clozapine may be an antagonist at a number of muscarinic receptors, the metabolite is an agonist. This is why we have people who are both constipated and drool at the same time. We’re getting the mixed properties of both the parent compound and the metabolite. The evidence that it’s the M1 effects comes from trials of pirenzepine which is an M1 selective anticholinergic agent available mostly in Europe. But there are case reports and case series of people who were administered pirenzepine and they seemed to block the sialorrhea induced by clozapine.
References
- Messer W, et al. Evidence for a preferential involvement of m1 muscarinic receptors in representational memory . Neurosci Lett 1990;116: 184-9.
- Chew M, et al. A model of anticholinergic activity of atypical antipsychotic medications . Schizophrenia Research 2006;88:63-72
- Bird AM, Smith TL, Walton AE. Current treatment strategies for clozapine-induced sialorrhea. Ann Pharmacother . 2011;45:667-75
- Gurrera RJ. Aspiration pneumonia an underappreciated risk of clozapine treatment . J Clin Psychopharm 2016; 36(2): 174-176
- Liang CS, et al. Comparison of the efficacy and impact on cognition of glycopyrrolate and biperiden for clozapine-induced sialorrhea in schizophrenic patients: a randomized, double-blind, crossover study . Schizophr Res. 2010;119(1-3):138.
