Dexfenfluramine, also marketed under the name Redux, is a serotoninergic anorectic drug. Dexfenfluramine, the dextrorotatory isomer of fenfluramine, is indicated for use in the management of obesity in patients with a body mass index of > or = 30 kg/m2, or > or = 27 kg/m2 in the presence of other risk factors. Unlike fenfluramine, dexfenfluramine is a pure serotonin agonist. Dexfenfluramine increases serotonergic activity by stimulating serotonin (5-hydroxytryptamine; 5-HT) release into brain synapses, inhibiting its reuptake into presynaptic neurons and by directly stimulating postsynaptic serotonin receptors. Dexfenfluramine reduces blood pressure, percent glycosylated hemoglobin, and concentrations of blood glucose and blood lipids, but these benefits may be indirect. Dexfenfluramine may also be of some value in controlling eating habits in diabetic patients, preventing weight gain after smoking cessation, and treating bulimia, seasonal affective disorder, neuroleptic-induced obesity, and premenstrual syndrome. Dexfenfluramine's most frequent adverse effects are insomnia, diarrhea, and headache; it has also been associated with primary pulmonary hypertension. The drug should not be combined with other serotonergic agonists because of the risk of serotonin syndrome. The recommended dosage is 15 mg twice daily. Dexfenfluramine is effective in the treatment of obesity in selected patients. Because its efficacy is lost after six months of continuous treatment, it should be viewed primarily as an adjunct to diet and exercise. Dexfenfluramine was approved by the FDA in 1996 and has been widely used for the treatment of obesity. However, Dexfenfluramine was removed from the U.S. market in 1997 following reports of valvular heart disease and pulmonary hypertension.

Trimebutine [3,4,5-trimethoxybenzoic acid 2-(dimethylamino)-2-phenylbutylester] is a noncompetitive spasmolytic agent. The actions of trimebutine on the gastrointestinal tract are mediated via (i) an agonist effect on peripheral mu, kappa and delta opiate receptors and (ii) release of gastrointestinal peptides such as motilin and modulation of the release of other peptides, including vasoactive intestinal peptide, gastrin and glucagon. Trimebutine attenuated colonic motility mainly through the inhibition of L-type Ca(2+) channels at higher concentrations, whereas, at lower concentrations, it depolarized membrane potentials by reducing BK(ca) currents, resulting in the enhancement of the muscle contractions.Trimebutine accelerates gastric emptying, induces premature phase III of the migrating motor complex in the intestine and modulates the contractile activity of the colon. It is indicated for the treatment and relief of symptoms associated with the irritable bowel syndrome (spastic colon); and in postoperative paralytic ileus in order to accelerate the resumption of the intestinal transit following abdominal surgery.

Trimebutine [3,4,5-trimethoxybenzoic acid 2-(dimethylamino)-2-phenylbutylester] is a noncompetitive spasmolytic agent. The actions of trimebutine on the gastrointestinal tract are mediated via (i) an agonist effect on peripheral mu, kappa and delta opiate receptors and (ii) release of gastrointestinal peptides such as motilin and modulation of the release of other peptides, including vasoactive intestinal peptide, gastrin and glucagon. Trimebutine attenuated colonic motility mainly through the inhibition of L-type Ca(2+) channels at higher concentrations, whereas, at lower concentrations, it depolarized membrane potentials by reducing BK(ca) currents, resulting in the enhancement of the muscle contractions.Trimebutine accelerates gastric emptying, induces premature phase III of the migrating motor complex in the intestine and modulates the contractile activity of the colon. It is indicated for the treatment and relief of symptoms associated with the irritable bowel syndrome (spastic colon); and in postoperative paralytic ileus in order to accelerate the resumption of the intestinal transit following abdominal surgery.

Trimebutine [3,4,5-trimethoxybenzoic acid 2-(dimethylamino)-2-phenylbutylester] is a noncompetitive spasmolytic agent. The actions of trimebutine on the gastrointestinal tract are mediated via (i) an agonist effect on peripheral mu, kappa and delta opiate receptors and (ii) release of gastrointestinal peptides such as motilin and modulation of the release of other peptides, including vasoactive intestinal peptide, gastrin and glucagon. Trimebutine attenuated colonic motility mainly through the inhibition of L-type Ca(2+) channels at higher concentrations, whereas, at lower concentrations, it depolarized membrane potentials by reducing BK(ca) currents, resulting in the enhancement of the muscle contractions.Trimebutine accelerates gastric emptying, induces premature phase III of the migrating motor complex in the intestine and modulates the contractile activity of the colon. It is indicated for the treatment and relief of symptoms associated with the irritable bowel syndrome (spastic colon); and in postoperative paralytic ileus in order to accelerate the resumption of the intestinal transit following abdominal surgery.

Trimebutine [3,4,5-trimethoxybenzoic acid 2-(dimethylamino)-2-phenylbutylester] is a noncompetitive spasmolytic agent. The actions of trimebutine on the gastrointestinal tract are mediated via (i) an agonist effect on peripheral mu, kappa and delta opiate receptors and (ii) release of gastrointestinal peptides such as motilin and modulation of the release of other peptides, including vasoactive intestinal peptide, gastrin and glucagon. Trimebutine attenuated colonic motility mainly through the inhibition of L-type Ca(2+) channels at higher concentrations, whereas, at lower concentrations, it depolarized membrane potentials by reducing BK(ca) currents, resulting in the enhancement of the muscle contractions.Trimebutine accelerates gastric emptying, induces premature phase III of the migrating motor complex in the intestine and modulates the contractile activity of the colon. It is indicated for the treatment and relief of symptoms associated with the irritable bowel syndrome (spastic colon); and in postoperative paralytic ileus in order to accelerate the resumption of the intestinal transit following abdominal surgery.

Cilnidipine (FRC-8653) is a dihydropyridine (DHP) type of calcium channel antagonist. The L-type Ca2+ channel blockade by cilnidipine affects predominantly vascular smooth muscle, thereby producing vasodilation of peripheral resistance vessels and coronary arteries. The blockade of N-type Ca2+ channels affects predominantly peripheral nerve endings of sympathetic neurons, thereby dilating blood vessels by lowering plasma catecholamine levels. Furthermore, renoprotective and neuroprotective effects as well as cardioprotective action of cilnidipine have been demonstrated in clinical practice or animal examinations. Cilnidipine was originated by Fuji & Rebio Pharmaceutical Co., Ltd. and developed jointly with Ajinomoto for the treatment of hypertension. Cilnidipine has been launched in Japan.

Timonacic or thioproline (4-Thiazolidinecarboxylic acid) is the product of condensation between cysteine and formaldehyde. Dietary timonacic slows the aging process in mammals and prolongs their life span. It exerts antioxidant and antineoplastic actions however its mechanism of action is elusive. Timonacic (brand names Heparegen or Arbitol) is used for the treatment of liver diseases.

Calcium dobesilate (brand name Doxium) is a veno-tonic drug, which is widely prescribed in more than 60 countries from Europe, Latin America, Asia and the Middle East for three main indications: chronic venous disease, diabetic retinopathy and the symptoms of haemorrhoidal attack. This drugs also in the phase III of clinical trial is an effective adjuvant therapy, with an absence of significant side-effects, in patients with venous ulcers and stasis dermatitis. It was suggested, that the inhibitory effect of calcium dobesilate on platelet function is mediated through the cyclic AMP pathway, and probably through activation of adenyl cyclase.

Pemafibrate (Parmodia®) is a novel, highly selective peroxisome proliferator-activated receptor (PPAR)-α modulator (SPPARM). It acts by binding to PPAR-α and regulating the expression of target genes that modulate lipid metabolism, thereby decreasing plasma triglyceride levels and increasing high-density lipoprotein cholesterol levels. Developed by Kowa Company, Ltd., oral pemafibrate has been approved in Japan for the treatment of hyperlipidaemia (including familial hyperlipidaemia). Pemafibrate is undergoing phase III development in a number of countries for the treatment of dyslipidaemias and is also in phase III development for the treatment of hypertriglyceridaemia.