Acetylcholine mimetics

Stimulation of postsvnaptic cholinergic receptors with so-called cholino-mimetics, i.e. compounds that can mimic some functions of acetylcholine at cholinergic synapses. This approach, which included experimental compounds such as RS 86 (Wettstein and Spiegel, 1984), xanomeline (Sramek et t//., 1995) and AF 102B (Fischer et t//., 1996), failed, possibly due to a lack of specificity of the molecules tested (Marin and Davis, 1998). 

Acetylcholine releasers, which can be viewed as mus-carino-mimetics, are experiencing similar difficulties. Linopirdine, that blocks a variety of channels including I, has been withdrawn from clinical trials (Kelly, 1999), while SM21 (Ghelardini et al., 1997) is still at the pre-clinical stage (Fig. 5). 

The alterations produced by THC and other cannabinoids in biogenic amine levels as well as on uptake, release and synthesis of neurotransmitters and effects on enzymes have been the subject of numerous investigations (for reviews see [8,52,55,114,115]). It is beyond the scope of the present summary to try to analyse and put into a proper perspective the wealth of data published so far. It is our subjective view that the mode of action of cannabi-mimetic compounds is somehow directly associated with prostaglandin metabolism (see, in particular, the series of papers by Burstein [115,116]), and/or reduction of hippocampal acetylcholine turnover observed in rats [117,118]. The latter effect is enantiospecific and follows the known SAR of the cannabinoids. This in vivo selectivity of action suggests that the THC may activate specific transmitter receptors which indirectly modulate the activity of the cholinergic neurons in the septalhippocampal pathway. 

Actions of angiotensin are mimetic of the motor actions of either acetylcholine or catecholamines. As discussed below, such actions are due to a direct effect of the peptide on the effector organ or to an indirect action through stimulation of the motor nerves or liberation of chemical transmitters at nerve endings. A brief description of these actions shall be given here. 

---