alpha-yohmbine (aka rauwloscine) is a diastereomer of yohimbine and shares many of the same properties. Rauwolscine acts as an alpha-2-adrenergic antagonist and is therefore used as an unregulated nutritional supplement for fat-burning and CNS stimulation. Rauwolscine is also an antagonist of the HT2B receptor and has been investigated for the potential to mitigate blood vessel spasms.

BMY-7378 is a multi-targeted inhibitor of α2C-adrenoceptor and α1D-adrenoceptor with pKi of 6.54 and 8.2, respectively, and acts as a mixed agonist and antagonist for 5-HT1A receptor with pKi of 8.3. BMY-7378 was at the preclinical stage of development for the treatment of anxiety disorders, but later was discontinued.

PNU-282987 is a potent and selective a7 nAChR agonist. This compound showed high affinity for the rat a7 nAChR (Ki = 26 nM) and activity at the a7–5-HT3 chimera (EC50 = 128 nM). In addition, PNU-282987 was found to be inactive at all tested monoamine, muscarine, glutamate, and GABA receptors at 1 uM concentration, except 5-HT3 receptors (Ki = 930 nM). The highly selective and potent a7 nAChR agonist PNU-282987 enhances GABAergic synaptic activity in the hippocampus in vitro, and reverses amphetamine induced auditory gating deficit in anesthetized rats. In addition, PNU-282987 improves the inherent gating deficit observed in a subset of rats and enhances amphetamine induced hippocampal activity. These results support the concept that a7 nAChR agonists represent a novel, potential pharmacotherapy in treatment of schizophrenia. It also has being shown that acute lung injury is reduced by PNU-282987 through changes in the macrophage profile.

A-582941 was found to exhibit high-affinity binding and agonism at alpha-7 nicotinic acetylcholine receptor (α7-nAChR), with acceptable pharmacokinetic properties and excellent distribution to the central nervous system. In vitro and in vivo studies indicated that A-582941 activates signaling pathways known to be involved in cognitive function such as ERK1/2 and CREB phosphorylation. A-582941 enhanced cognitive performance in behavioral assays including the monkey delayed matching-to-sample, rat social recognition, and mouse inhibitory avoidance models that capture domains of working memory, short-term recognition memory, and long-term memory consolidation, respectively. AbbVie is developing α7-nAChR agonists including A-582941 as neuroprotective agents for the treatment of cognitive disorders such as Alzheimer's disease and schizophrenia. Development is at the preclinical stage.