The in vivo muscarinic receptor binding of antimuscarinic agents (oxybutynin, solifenacin, tolterodine, and imidafenacin) used to treat urinary dysfunction in patients with overactive bladder is reviewed. Transdermal administration of oxybutynin in rats leads to significant binding of muscarinic receptors in the bladder without long-term binding in the submaxillary gland and the abolishment of salivation evoked by oral oxybutynin. Oral solifenacin shows significant and long-lasting binding to muscarinic receptors in mouse tissues expressing the M3 subtype. Oral tolterodine binds more selectively to muscarinic receptors in the bladder than in the submaxillary gland in mice. The muscarinic receptor binding of oral imidafenacin in rats is more selective and longer-lasting in the bladder than in other tissues such as the submaxillary gland, heart, colon, lung, and brain, suggesting preferential muscarinic receptor binding in the bladder. In vivo quantitative autoradiography with (+)N-[11C]methyl-3-piperidyl benzilate in rats shows significant occupancy of brain muscarinic receptors with the intravenous injection of oxybutynin, solifenacin, and tolterodine. The estimated in vivo selectivity in brain is significantly greater for solifenacin and tolterodine than for oxybutynin. Imidafenacin occupies few brain muscarinic receptors. Similar findings for oral oxybutynin were observed with positron emission tomography in conscious rhesus monkeys with a significant disturbance of short-term memory. The newer generation of antimuscarinic agents may be advantageous in terms of bladder selectivity after systemic administration.
Administration, Cutaneous ; Animals ; Autoradiography ; Benzhydryl Compounds ; Brain ; Colon ; Cresols ; Heart ; Humans ; Imidazoles ; Injections, Intravenous ; Lung ; Macaca mulatta ; Mandelic Acids ; Memory, Short-Term ; Mice ; Muscarinic Antagonists ; Phenylpropanolamine ; Positron-Emission Tomography ; Quinuclidines ; Rats ; Receptors, Muscarinic ; Salivation ; Solifenacin Succinate ; Submandibular Gland ; Tetrahydroisoquinolines ; Tolterodine Tartrate ; Urinary Bladder ; Urinary Bladder, Overactive

Background: Hot spring inhalation and rock bathing are widely practiced in Europe, and immersion in water up to the shoulders is popular in Japanese balneotherapy. We designed a combination therapy of steam rock bathing and immersion in an open-air hot spring pool for allergic rhinitis.Methods: Data were obtained by anonymous questionnaires from 19 participants with perennial allergic rhinitis who underwent the combination therapy for several days during the spring-pollen season. The participants immersed themselves in a sitting position in Saiboku hot spring water (sodium salt hot spring) at 41°C up to the shoulder level for 10 min in the open-air and then lay on a floor paved with small rocks in a supine position for 20 min in a room filled with the steam from hot springs, then immersed themselves again in the hot spring water for 10 min, and finally rested and sat on a chair for 20 min in a comfortable room. The hot spring water circulated through tubes with small holes that were embedded under the floor, which was paved with small rocks consisting of tourmaline and lime stones. Steam from the hot spring water penetrated through the floor and vaporized in the room. The rock bathing room was 40°C in temperature and 75% in humidity.Results: Clinical symptoms were alleviated in 17 of 19 participants. Watery rhinorrhea, eye itching, sneeze, and sore throat were improved in 100%, 75%, 40%, and 100% of the participants, respectively, compared with symptoms during the previous several years. No adverse effects were observed in any participants. Conclusion: Steam rock bathing, combined with immersion in an open-air hot spring pool, is useful in ameliorating the focal and systemic symptoms of allergic rhinitis.