JNJ-39393406 is a positive allosteric alpha-7 nicotinic acetylcholine receptor modulator. It was under development for the treatment of smoking cessation, schizophrenia, Alzheimer's disease, but development for these indications was discontinued.

Otenzepad is the first competitive muscarinic M2 antagonist that is cardioselective and had been in phase III clinical trials for the treatment of arrhythmias and bradycardia. Otenzepad was originally developed by Boehringer Ingelheim Pharma KG (Boehringer Ingelheim) in Germany. The parent company is developing oral and IV formulations of the drug for use in symptomatic bradycardia, sinus bradycardia, sick sinus syndrome and symptomatic arrhythmias after intoxication. However, all these research has been discontinued. Otenzepad binds to muscarinic cholinergic receptors in a simple competitive manner. Its affinity for cardiac (M2) muscarinic receptors is about 7 times greater than for ganglionic (M1) receptors and about 36 times greater than for glandular (M3) receptors. The (+)-enantiomer of otenzepad is about 8 times more potent at M2-receptors than the (−)-enantiomer. In a double-blind study, 48 healthy male volunteers were randomised to single oral doses of placebo or otenzepad (120, 240 or 480mg). Heart-rate (HR) was significantly increased by the 250 and 480mg doses (by 15 and 21 beats/minute, respectively). The 480mg dose also increased Diastolic Blood Pressure (DBP) significantly compared with placebo. The oral pharmacokinetics of otenzepad were investigated in a double-blind study in which 48 healthy male volunteers were randomised to single oral doses of placebo or otenzepad (120, 240 or 480mg). Otenzepad bioavailability was 45%, mean residence time (MRT) was 12.5 hours and tmax occurred 2.5 hours postdose.

CP-601927 is a selective α4β2 nicotinic acetylcholine receptor partial agonist developed by Pfizer. The compound has antidepressant-like activity in animal models and was investigated in a phase 2 trial as an augmentation to other antidepressant therapy in patients with Major Depressive Disorder. However, CP-601927 ultimately lacked efficacy as an adjuvant in these patients because of insufficient activity of α4β2 at therapeutic doses.

(±)-quinuclidinyl benzilate (3-quinuclidinyl benzilate), is a specific muscarinic cholinergic receptor antagonist. It binds potently but reversibly to the muscarinic cholinergic receptors of mammalian brain and peripheral tissues. 3-quinuclidinyl benzilate was invented by Hoffmann-La Roche Inc in 1951, while investigating antispasmodic agents resembling tropine for the treatment of gastrointestinal conditions. In the 1960s 3-quinuclidinyl benzilate, was developed and weaponized as a new chemical agent for battlefield use as a psychochemical. Assigned the NATO code BZ it is classified as a hallucinogenic chemical warfare agent that affects both the peripheral and central nervous systems (CNS). It is one of the most potent anticholinergic psychomimetics known, with only small doses necessary to produce incapacitation. The primary route of absorption is through the respiratory system but absorption also can occur through the skin or gastrointestinal tract. BZ is odorless and is usually disseminated as an aerosol. Data regarding the health effects of BZ in humans following inhalation exposure are limited to military application studies. Pharmacologic activity of 3-quinuclidinyl benzilate is similar to other anticholinergic drugs (eg, atropine) but with a much longer duration of action. It was shown that I[3H]-3-quinuclidinyl benzilate accumulated in various brain regions after intravenous injection. The specific binding of [3-3H]3-quinuclidinyl-benzilate and [125I]3-quinuclidinyl-(3-iodo-4-hydroxy-benzilate) to rat brain subcellular fractions is parallel in myelin, synaptic plasma membrane and mitochondrial fractions with a 3-4-fold enrichment observed in synaptic plasma membrane over crude mitochondrial fractions. These findings suggested the use of 3-quinuclidinyl benzilate as a binding probe useful in assaying low levels of muscarinic receptor in tissue culture and other biological sources including labeling the receptor in vivo for autoradiographic studies. M2 muscarinic acetylcholine receptor (M2 receptor), essential for the physiologic control of cardiovascular function through activation of G protein-coupled inwardly-rectifying potassium channels, was shown to bind 3-quinuclidinyl benzilate with high affinity in vitro.