Comparative X-Ray study of galantamine and tacrine on the evacuatory function of rat gastrointestinal tract

Abstract

<jats:title>Abstract</jats:title><jats:p>A The acetylcholinesterase inhibitors galantamine and tacrine are used to treat Alzheimer’s disease. However, these compounds also affect the gastrointestinal (GI) tract. Here, we compared and analyzed both the effects of galantamine-and tacrine on the evacuatory kinetics of the GI tract in rats. Rats were untreated (n=15) or treated with galantamine (one daily dose of 1 mg/kg per os for 21 days; n=17) or tacrine (one daily dose of 0.5 mg/kg per os for 21 days; n=13) and evacuatory kinetics were assessed using radiological methods. Galantamine initially slowed and then accelerated evacuation, which is characteristic of the majority of cholinesterase inhibitors and is a result of the endogenous acetylcholine accumulated in the GI tissues. In the tacrine-treated rats the contrast medium was kept in the stomach and cecum and its evacuation time was reliably increased. These results indicate that when administered for 20 days, galantamine and tacrine have different effects on motor and evacuatory function in the GI tract of rats, because at certain levels of the tract the tacrine-action is dominated by specific non-cholinergic and non-anticholinesterase mechanisms.</jats:p>

Tacrine-induced tachyphylaxis in gastric smooth muscles

“…[3,4]. Some of these adverse drug reactions result from non-anticholinesterase or non-cholinergic mechanisms of action [5] on GI tract smooth muscles (SM). These mechanisms can either reduce or enhance the effect caused by the central anticholinesterase action of tacrine.…”

Sensitizing Effect of Tacrine on M-Cholinergic Receptors in Gastric Smooth Muscle of Rats

“…The effects that tacrine exerts on the motility and evacuation functions of the gastrointestinal (GI) tract are particularly strongly pronounced; these effects are results of the action the high level of endogenous acetylcholine has on the gastrointestinal smooth muscles (SM). 2,3 It is well known that the anti-cholinesterase ef-fect does not exhaust all possibilities of the primary pharmacological reaction which accounts for the therapeutic and diverse effects of tacrine. The effects which are result from the non-anti-cholinesterase and even the non-cholinergic mechanisms are also well expressed.…”

Participation of cAMP in tacrine-induced gastric smooth muscle relaxation

“…It is a result from the direct action of tacrine over the contractile apparatus of the gastrointestinal smooth muscles [14]. When applied in vivo (daily dose 0.5 mg/kg) the drug significantly influences the motility of GI tract, causing hypotension, inhibited peristaltic activity and retarded evacuatory kinetics [12,16]. This influence, untypical of acetylcholinesterase inhibitors, indicates a significant presence of non-anticholinesterase mechanisms in the formation of the total drug effect and most likely accounts for its specific side effects on GI tract motility [12,16,17].…”