Alzheimer's drug design based upon an invertebrate toxin (anabaseine) which is a potent nicotinic receptor agonist.

Naturally occurring toxins can often serve as useful chemical tools for investigating signalling processes in nervous and other systems. Tetrodotoxin and alpha-bungarotoxin are prime examples of toxins which are widely used in neurobiological research. Some toxins may also become molecular models for designing new drugs. Usually drugs are small, non-peptide molecules, as these display better bioavailability, longer durations of action and are less likely to generate immune responses. The relatively large size and conformational flexibility of peptides and protein toxins makes them more challenging molecular models for rational drug design. This article considers a marine invertebrate toxin, anabaseine, and describes how manipulation of the structure of this alkaloid has provided a drug candidate which selectively stimulates mammalian brain alpha7 nicotinic receptors. Numerous anabaseine analogs were synthesized and subjected to a variety of pharmacological, behavioral and toxcicological tests. This led to the choice of GTS-21 (also known as 3-(2,4-dimethoxybenzylidene)-anabaseine or DMXBA), as a drug candidate for the treatment of Alzheimer's dementia. The chemical and pharmacological properties of GTS-21 are compared with those of the initial lead compound, anabaseine.

[Results of clinical investigation of anti-nicotine drug patches]. / Rezultaty klinicheskogo izucheniia antinikotinovykh lekarstvennykh plenok.

The paper gives the results of clinical trials of antinicotinic therapeutical films containing anabasinum, cytisinum or their combination in equal ratios. They were used in 74 patients with chronic nicotinism. The level of the drug in a film was 1.5 gm. The mode of its application was to apply it to the gingiva beneath the upper lip. The biosoluble polymer carrier-based antinicotinic films are easy-to-use and rather effective in the control of smoking. The films produced effects in 75.8% of patients, including a full effect, i.e. a full refusal of smoking in 46.8%. The films in combination with cytisinum and anabasinum, or those with cytisinum alone was the most effective. There were no adverse reaction when the films were applied. The drug is well tolerated by patients with coronary heart disease, arterial hypertension, and diabetes mellitus.