Trifluperidol is an antipsychotic butyrophenone derivative. It is a high-affinity sigma receptor blocker and it was strongly selective for NR1a/2B receptors. It exhibit pharmacological effects and a mechanism of action very similar to that of phenothiazines and thioxanthenes in that it blocks dopaminergic receptors. It is more selective with respect to D2 receptors. Trifluperidol is indicated for the treatment of acute and chronic schizophrenia, mania and hypomania, organic psychoses, childhood behavioral disorders, agitation in psychotic illness and motor tics. Trifluperidol has been suspected as a cause of cataract in Japan. Patients receiving trifluperidol treatment may develop a parkinsonian-like syndrome which responds to withdrawal of the drug or concurrent administration of an anti-parkinsonian drug. Acute dystonias and akathisia are other acute extrapyramidal effects; tardive dyskinesia may supervene after longer periods of treatment.

Ipidacrine (Neiromidin) is a drug first synthesized by the National Research Center for Biologically Active Compounds in the Russian Federation. Neuromidin has a direct stimulating effect on the conduct of the pulse along the nerve fibers, interneuronal and neuromuscular synapses of the CNS and peripheral nervous system. Pharmacological action neuromidin is based on a combination of two mechanisms of action: blockade of potassium channels of the membrane of neurons and muscle cells; reversible inhibition of cholinesterase in synapses. Neuromidin enhances the effect on smooth muscle acetylcholine not only, but epinephrine, serotonin, histamine and oxytocin. It has the following pharmacological effects: - Improve and stimulate impulse conduction in the nervous system and neuromuscular transmission; - Enhances contractility of smooth muscle organs under the influence of acetylcholine agonists, adrenaline, serotonin, histamine and oxytocin receptors, with the exception of potassium chloride; - Improves memory, slows progressive course of dementia. In preclinical studies Neuromidin is not teratogenic, embryotoxic, mutagenic, carcinogenic and immunotoxic action, had no effect on the endocrine system

Suloctidil is considered to be calcium antagonist. In addition to its vascular antispasmodic activity, suloctidil affects blood platelets and enhances brain energy metabolism. Suloctidil was being evaluated in many clinical trials for use in dementia and thrombotic disorders. Suloctidil induces hepatotoxicity.

Bepridil (trade name Vascor) is an amine calcium channel blocker used to treat angina. Bepridil is a calcium channel blocker that has well characterized anti-anginal properties and known but poorly characterized type 1 anti-arrhythmic and anti-hypertensive properties. It is not related chemically to other calcium channel blockers such as diltiazem hydrochloride, nifedipine and verapamil hydrochloride. Bepridil has inhibitory effects on both the slow calcium (L-type) and fast sodium inward currents in myocardial and vascular smooth muscle, interferes with calcium binding to calmodulin, and blocks both voltage and receptor operated calcium channels. Bepridil inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. This has been demonstrated in isolated myocardial and vascular smooth muscle preparations in which both the slope of the calcium dose response curve and the maximum calcium-induced inotropic response were significantly reduced by bepridil. In cardiac myocytes in vitro, bepridil was shown to be tightly bound to actin. Bepridil regularly reduces heart rate and arterial pressure at rest and at a given level of exercise by dilating peripheral arterioles and reducing total peripheral resistance (afterload) against which the heart works. Bepridil is no longer sold in the United States, but it is still marketed in other countries. Bepridil has antihypertensive and selective anti-arrhythmia activities and acts as a calmodulin antagonist. Although, it contains one chiral center, it is generally administered as a racemates. The drug bepridil is a racemic mixture of two enantiomers for the 2R as CID 16048570 and 2S as CID 445143. (R)-isomer of bepridil is more active than (-S)- isomer, in certain cases. In the retrogradely perfused, paced rat heart the higher activity was found for the ( )-enantiomer, which was 4.27 times more potent in increasing coronary flow than the (-)-isomer. The two enantiomers of bepridil showed a lower activity on maximum systolic left ventricular pressure (MSLVP) than on coronary flow, and a similar 3-4 fold stereoselectivity with both parameters.

(R)-Lercanidipine is enantiomer of antihypertensive drugs Lercanidipine, that acts by blocking L-type calcium channels, allowing relaxation and opening of blood vessels. The dihydropyridine calcium antagonists promote systemic vasodilatation by a reversible blockade of voltagedependent Ca2+ influx through L-type channels in the cell membrane. (S)-Lercanidipine has 100- to 200-fold greater affinity than the (R)-enantiomer for the L-type calcium channel. The pharmacokinectics of (S)- Lercanidipine has been evaluated in healthy volunteers, in elderly and non-elderly patients with hypertension, and in patients with renal or hepatic impairment. Patients from these studies were investigated after receiving a single 10 or 20 mgdose of [14C]-labeled rac-Lercanidipine as a solution. The maximum plasma concentrations of (S)-Lercanidipine were reached within 2–3 h and the area under the plasma concentration–time curves were not linearly related to the dose, indicating a saturable first-pass metabolism. The absorption of (S)-LER increases after the ingestion of a highfat meal. Lercanidipine is highly bound to plasma protein (>98%) in humans. Its volume of distribution of 2–2.5 L/kg was determined in healthy volunteers after intravenous infusion of 2 mg. Lercanidipine is extensively metabolized by CYP 3A4 to inactive pyridine derivatives. A crossover study involving a single administration of either 10 mg of (R)- or (S)-LER or 20 mg of rac-LER as a solution demonstrated no in vivo enantiomer interconversion

(S)-Lercanidipine is enantiomer of antihypertensive drugs Lercanidipine, that acts by blocking L-type calcium channels, allowing relaxation and opening of blood vessels. The dihydropyridine calcium antagonists promote systemic vasodilatation by a reversible blockade of voltage-dependent Ca2+ influx through L-type channels in the cell membrane. (S)-Lercanidipine has 100- to 200-fold greater affinity than the (R)-enantiomer for the L-type calcium channel. The pharmacokinetics of (S)- Lercanidipine has been evaluated in healthy volunteers, in elderly and non-elderly patients with hypertension, and in patients with renal or hepatic impairment. Patients from these studies were investigated after receiving a single 10 or 20 mg dose of [14C]-labeled rac-Lercanidipine as a solution. The maximum plasma concentrations of (S)-Lercanidipine were reached within 2–3 h and the area under the plasma concentration-time curves were not linearly related to the dose, indicating a saturable first-pass metabolism. The absorption of (S)-LER increases after the ingestion of a high-fat meal. Lercanidipine is highly bound to plasma protein (>98%) in humans. Its volume of distribution of 2–2.5 L/kg was determined in healthy volunteers after intravenous infusion of 2 mg. Lercanidipine is extensively metabolized by CYP 3A4 to inactive pyridine derivatives. A crossover study involving a single administration of either 10 mg of (R)- or (S)-LER or 20 mg of rac-LER as a solution demonstrated no in vivo enantiomer interconversion

Manidipine, (S)- is enantiomer of Manidipine a lipophilic, third-generation dihydropyridine calcium channel antagonist with a high degree of selectivity for the vasculature, thereby inducing marked peripheral vasodilation with negligible cardiodepression. Manidipine has different pharmacological effects and (S)-manidipine is shown to be about 30–80 times more potent than (R)-manidipine in its antihypertensive action and in the radioligand binding assay. Patch-clamp experiments revealed that the S-enantiomers of manidipine displayed a faster onset of action and produced a greater blockade than the R-enantiomer. Also, manidipine enantiomers have markedly different pharmacokinetics and the S/R ratio for (S)- and (R)-enantiomer concentrations is 2.0

Manidipine, (R)- is enantiomer of Manidipine a lipophilic, third-generation dihydropyridine calcium channel antagonist with a high degree of selectivity for the vasculature, thereby inducing marked peripheral vasodilation with negligible cardiodepression. Manidipine has different pharmacological effects and (S)-manidipine is shown to be about 30–80 times more potent than (R)-manidipine in its antihypertensive action and in the radioligand binding assay. Patch-clamp experiments revealed that the S-enantiomers of manidipine displayed a faster onset of action and produced a greater blockade than the R-enantiomer. Also, manidipine enantiomers have markedly different pharmacokinetics and the S/R ratio for (S)- and (R)-enantiomer concentrations is 2.0

Azelnidipine is a dihydropyridine calcium channel antagonist being jointly developed by Daiichi Sankyo Inc (formerly Sankyo) and Ube Industries. Azelnidipine is a L-type calcium channel antagonist. Azelnidipine was approved by Pharmaceuticals and Medicals Devices Agency of Japan (PMDA) on Jan 31, 2003. Azelnidipine is indicated for the treatment of hypertension. Its trend name is Calblock. Azelnidipine has two enantiomers (R-(−)- and S-( )-enantiomers) due to an asymmetric carbon at the 4-position, and the (R)-(−) enantiomer of dihydropyridine calcium antagonists is considered to possess intrinsic pharmacological activity. The pharmacological action of azelnidipine resides in the (R)-enantiomer. This is in marked contrast to other calcium channel blocker (CCB) in which the (S)-enantiomer is responsible for the biological activity. There were no significant differences in the inhibitory effects on TGF-b1-induced expression of COL1A1 mRNA among vitamin E - pretreated LX-2 cells treated with azelnidipine (racemate), (R)-(-)-azelnidipine or (S)-( )-azelnidipine, although the L-type voltage-operated calcium channel blocking activity of (R)-(-)- enantiomer was more potent than that of the (S)-( )- enantiomer.

Azelnidipine is a dihydropyridine calcium channel antagonist being jointly developed by Daiichi Sankyo Inc (formerly Sankyo) and Ube Industries. Azelnidipine is a L-type calcium channel antagonist. Azelnidipine was approved by Pharmaceuticals and Medicals Devices Agency of Japan (PMDA) on Jan 31, 2003. Azelnidipine is indicated for the treatment of hypertension. Its trend name is Calblock. Azelnidipine has two enantiomers (R-(−)- and S-( )-enantiomers) due to an asymmetric carbon at the 4-position, and the (R)-(−) enantiomer of dihydropyridine calcium antagonists is considered to possess intrinsic pharmacological activity. The pharmacological action of azelnidipine resides in the (R)-enantiomer. This is in marked contrast to other calcium channel blocker (CCB) in which the (S)-enantiomer is responsible for the biological activity. There were no significant differences in the inhibitory effects on TGF-b1-induced expression of COL1A1 mRNA among vitamin E - pretreated LX-2 cells treated with azelnidipine (racemate), (R)-(-)-azelnidipine or (S)-( )-azelnidipine, although the L-type voltage-operated calcium channel blocking activity of (R)-(-)- enantiomer was more potent than that of the (S)-( )- enantiomer.