Tioperidone is tranquilizer. This antidepressant agent reverses P-glycoprotein-mediated multidrug resistance.

Tubulozole is a stereospecific microtubule inhibitor. Structurally it is related to the benzimidazole carbamates by its carbamate moiety, which is essential for the activity of both types of compounds. The compound exists as a cis-isomer called tubulozole-C (R 46 846) and as a trans-isomer called tubulozole-T. The cis-isomer appears to be a potent and specific microtubule inhibitor, the trans-isomer being inactive at 100 times higher concentrations. At low concentrations, both isomers of tubulozole (C, T) inhibit Plasmodium falciparum but only tubulozole C inhibits mammalian cells. Since tubulozole C prevents polymerization of mammalian tubulin whereas tubulozole T does not, the antimalarial action of tubulozoles may not involve microtubules. Tubulozole-C, a new synthetic anticancer drug, interfered with the structure and function of microtubules in both interphase and mitotic cells. The activity of Tubulozole-C in experimental tumor systems can be explained partly by a direct antimitotic effect and partly by the disintegration of the normal subcellular organization of the nondividing cells. At concentrations which affect the microtubule system, tubulozole-C arrested directional migration of transformed cells and malignant invasion in a three-dimensional organ culture system. Investigations in vivo show that malignant L1210 leukemia cells are more susceptible to the antimicrotubular effect of tubulozole-C than are the normal leukocytes of the host. The trans-isomer of tubulozole (tubulozole-T, R 48 265), which has no antitumor activity in vivo, did not affect the microtubule system of cells in vitro or their capacity for directional migration or for malignant invasion.

Piridronic acid is pyridinyl bisphosphonate. It is the bone calcium metabolism regulator. Piridronic acid was used for the treatment of osteoporosis. It is the human farnesyl pyrophosphate synthase inhibitor. When expressed on an actual or anticipated clinical dose basis for osteoporosis piridronic acid may have a greater potential for inducing gastric damage than do pyridinyl bisphosphonates. Piridronic acid induced significantly more antral damage than risedronate and a greater number of lesions compared to pamidronate and risedronate.

Suronacrine (also known as HP128) is a tetrahydroacridinol derivative patented by Hoechst-Roussel Pharmaceuticals, Inc for the treatment of various memory dysfunctions characterized by decreased cholinergic function. The activity ofHP128 is attributable to its inhibition of both norepinephrine uptake and cholinesterase enzyme activity. Suronacrine has enhanced memory in animals with combined cholinergic and adrenergic lesions. In preclinical models, Suronacrine blocks responses to nerve stimulation and to carbachol, but increased responses to acetylcholine. Extracellular recording of nerve terminal currents from triangularis sterni preparations revealed that Suronacrine had a selective blocking action on the waveform associated with K+ currents.

Indotecan (LMP400) is a novel indenoisoquinoline derivative with specific topoisomerase I inhibition activity, developed by Division of Cancer Treatment and Diagnosis National Cancer Institute for cancer treatment. In preclinical studied Indotecan inhibited the cell growth of established mouse pheochromocytoma cell lines and primary human tumor tissue cultures. Low doses of Indotecan decreased the protein levels of hypoxia-inducible factor 1 (HIF-1α), one of a family of factors studied as potential metastatic drivers in these tumors. In vitro, Indotecan showed an increase in the growth-inhibitory effects in combination with other chemotherapeutic drugs that are currently used for the treatment of pheochromocytoma. Recently Indotecan has entered Phase I clinical trials for the treatment of cancer patients at the National Cancer Institute, and definite plans are being formulated to commence Phase II clinical trials.

Camiglibose is a glucopyranoside and inhibitor of alpha-glucosidase with antihyperglycemic activity patented by Merrell Dow Pharmaceuticals. In rats, a single oral dose of Camiglibose administered simultaneously with 2 g/kg body wt sucrose resulted in a dose dependent reduction in the area under the 0- to 3-h glycemic response curve, A reduction in the glycemic response to sucrose was accompanied by reduced insulin secretion. Camiglibose was more effective against a sucrose load in streptozocin-administered rats than in control rats and was as effective after 16 daily doses as after a single dose. Doses that reduced the glycemic response to carbohydrate did not inhibit liver lysosomal a-glucosidase activity or cause lysosomal glycogen accumulation. In cynomolgus monkeys, an oral dose of 1 mg/kg Camiglibose reduced the glycemic and insulin responses to sucrose

BMS-863233, also known as XL413, is a potent and selective cell division cycle 7 (CDC7) kinase inhibitor with potential antineoplastic activity. BMS-863233 binds to and inhibits the activity of CDC7, which may result in the inhibition of DNA replication and mitosis, the induction of tumor cell apoptosis, and the inhibition of tumor cell proliferation in CDC7-overexpressing tumor cells. CDC7, a serine-threonine kinase overexpressed in a variety of tumor cell types, plays an essential role in the initiation of DNA replication by activating origins of replication.

Cicloprolol is a beta-adrenoceptor antagonist patented by French pharmaceutical company Synthelabo S. A. for treatment of heart disorders. Cicloprolol has a weak beta-agonistic effect at normal levels of adrenergic discharge and acts as an antagonist at high levels of discharge. In clinical trials, Cicloprolol did not affect resting heart rate and blood pressure, but it reduced significantly peak exercise heart rate and peak rate-pressure product. The effect was especially significant in patients with sinus rhythm. The drug did not induce bradycardia or arrhyth- mias. Resting and exercise ejection rate were not affected. Cicloprolol improved the quality of life and the work capacity of 40% of patients with congestive failure due to ischemic etiology. Side effects were few and similar to placebo and cicloprolol.

Clodazon (AW 142446) is an antidepressant drug investigated in Germany in the 1960s. In animal models, clodazon inhibits the catalepsy induced by tetrabenazine and it potentiates the effect of catecholamines, both effects being of the order experienced with imipramine. In clinical trials, about 2/3 of the patients showed a positive antidepressive effect with few side effects.

Conessine is a plant steroid alkaloid that acts as a potent and specific antagonist of histamine H3 receptors. Conessine displayed high affinity at both rat and human H3 receptors (pKi = 7.61 and 8.27) and generally high selectivity against other sites, including histamine receptors H1, H2, and H4. Conessine was found to efficiently penetrate the CNS and reach very high brain concentrations. Although the very slow CNS clearance and strong binding to adrenergic receptors discouraged focus on conessine itself for further development, its potency and novel steroid-based skeleton motivated further chemical investigation. Modification based on introducing diversity at the 3-nitrogen position generated a new series of H3 antagonists with higher in vitro potency, improved target selectivity, and more favorable drug-like properties. Conessine also has high affinity for the adrenergic receptors. Conessine has being shown to possess anti-malarial activity. In India conessine finds therapeutic use for treatment of dysentery and helminthic disorders.