Study summary · research use only
Parasympathetic vasoactive intestinal peptide (VIP): a likely contributor to clozapine-induced sialorrhoea
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This rat study examined whether the parasympathetic transmitter vasoactive intestinal peptide (VIP) contributes to clozapine-induced sialorrhoea, testing individual and combined intravenous doses of VIP and clozapine. Saliva was collected from denervated parotid glands, and saliva and blood from innervated submandibular glands, in adrenoceptor antagonist-pretreated, pentobarbitone-anaesthetised rats. The authors reported that the submandibular volume response to the combination was 2-3 times higher than to VIP alone, while blood pressure and glandular blood flow did not differ from those to VIP alone, and the synergism occurred independent of nerves as shown in denervated parotid glands. The authors speculate that VIP of parasympathetic origin, through synergistic interaction with clozapine, may contribute to clozapine (muscarinic M1-receptor)-induced sialorrhoea in schizophrenics.
Abstract
The parasympathetic transmitter vasoactive intestinal peptide (VIP) increases salivary gland blood flow and evokes protein secretion and, in some species, such as rats, a small fluid secretion. It interacts synergistically with muscarinics for protein and fluid output. Human salivary acini are supplied with VIP-containing nerves. We hypothesise that VIP and clozapine, acting together, evoke a volume of saliva greater than the sum of those induced by each drug given separately. It was further considered whether, in the current test situation, circulatory events influenced the magnitude of the secretory response. Saliva from parotid glands deprived of their autonomic innervation, and saliva and blood from innervated submandibular glands were collected in adrenoceptor antagonist-pretreated pentobarbitone-anaesthetised rats. Initially, the individual and then the combined effects of intravenous doses of VIP and clozapine were established. The submandibular volume response to the combination was 2-3 times higher, while blood pressure and glandular blood flow did not differ from those to VIP alone. The synergism occurred independent of nerves as shown in denervated parotid glands. From the current preclinical data, we speculate that VIP of parasympathetic origin, by its synergistic interaction with clozapine, may contribute to the clozapine (muscarinic M1-receptor)-induced sialorrhoea in schizophrenics.
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