Lithium inhibits substance P and vasoactive intestinal peptide-induced relaxations on isolated porcine ophthalmic artery.

Lithium is currently a major drug used as a treatment for affective disorders and cluster headache, among other conditions. Its mechanism of action remains unknown. The trigeminovascular system may be involved in the pathophysiology of cluster headache and related diseases by liberating neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) in the eye-forehead region. The objective of this study was to investigate whether or not a low concentration of lithium may interfere with peptidergic neuro-transmission at this level. Vasoactive intestinal peptide (VIP), SP, CGRP, capsaicin, and SP+CGRP concentration-response relaxation curves were obtained in the presence and absence of 2 x 10(-4) M lithium in isolated porcine ophthalmic arteries. Lithium inhibited the SP and VIP, but not the CGRP responses. Capsaicin-(a neurotoxin causing release of stored sensory neuropeptides) induced relaxations were partially inhibited by lithium. It is concluded that lithium may interfere with SP- and VIP-induced relaxation. If SP and VIP are of pathogenic significance in cluster headache, lithium may possibly work by counteracting unwanted effects of such peptides.