Pharmacological profiles

Pharmacological Profiles of Anxiolytics and Sedative—Hypnotics. Historically, chemotherapy of anxiety and sleep disorders rehed on a wide variety of natural products such as opiates, alcohol, cannabis, and kawa pyrones. Use of various bromides and chloral derivatives ia these medical iadications enjoyed considerable popularity early ia the twentieth century. Upon the discovery of barbiturates, numerous synthetic compounds rapidly became available for the treatment of anxiety and insomnia. As of this writing barbiturates are ia use primarily as iajectable general anesthetics (qv) and as antiepileptics. These agents have been largely replaced as treatment for anxiety and sleep disorders. 

The pharmacological profile of buspirone in both animals and humans differs substantially from that of the ben2odia2epine anxiolytics. Buspirone lacks anticonvulsant, myorelaxant, and hypnotic effects. It also produces less sedation resulting in less psychomotor impairment in conjunction with... 

Included in the noimarcotic class of antitussives are many compounds that do not possess a morphine skeleton and which vary widely from each other with respect to stmctural features and pharmacologic profiles. 

Oxolamine [959-14-8] (57) is sold in Europe. It is an oxadiazole, and its general pharmacological profile is described (81). The compound possesses analgesic, antiinflammatory, local anesthetic, and antispasmodic properties, in addition to its antitussive activity. Although a central mechanism may account for some of the activity, peripheral inhibition of the cough reflex may be the dominant effect. The compound has been shown to be clinically effective, although it is less active than codeine (82,83). The synthesis of oxolamine is described (84). 

Ethyl dibunate [5560-69-0] (59), which is sold ia Canada, is the ethyl ester of 3,6-(/ f2 -butyl)-l-naphthalenesulfonic acid. It is stmcturaHy unrelated to most of the classical antitussives and is a selective central inhibitor of the cough reflex. Also significant is its low toxicity. The oral LD q is greater than 5000 mg/kg in the rat. The clinical and pharmacological profile of this compound has been reviewed (89). 

Except for the addiction HabiUty of some of the narcotic antitussives, side effects for most of the centrally acting compounds are relatively few and mild at therapeutic doses. QuaUtative comparisons of both side effects and pharmacological profiles have been summarized for many of the compounds described above (97). 

Extension of the alkyl group on the carbon bearing the amine changes the pharmacologic profile. Reductive amination of 1-phenylbutanone-2 (60) with pyrrolidine in formic acid gives pro-litane (61), a central nervous system stimulant agent with antidepressant properties. 

It should be noted that the stereochemistry of the B/C and C/D junctions has remained inviolate in all the modifications discussed to date. It was in fact assumed that changing either of these was a quick path to loss of activity. Just such a modification, however, led to a progestin with a unique pharmacologic profile. 

Installation of a different side chain completely alters the pharmacological profile leading to a new class of muscle relaxants. The synthesis begins with copper(II)-promoted di-azonium coupling between furfural (j ) and 3,4-dichlorobenzene-diazonium chloride (15) to give bi aryl aldehyde Next, condensation with 1-aminohydantoin produces the muscle relaxant clodanolene (17). ... 

Nabitan (39) is a cannabis-inspired analgesic whose nitrogen atom was introduced in order to improve water solubility and perhaps to affect the pharmacological profile as well. The phenolic hydroxyl of benzopyran synthon is esterified with 4-(l-piperidino)butyric acid under the influence of dicyclohexyl carbodi mi de. In addition to being hypotensive and... 

Whitebread, S., Hamon, J., Bojanic, D., and Urban, L. (2005). In vitro safety pharmacology profiling An essential tool for successful drug development. Drug Disc. Today 10 1421-1433. 

Meuleman DG. Orgaran (Org 10172) its pharmacological profile in animal models. Haemostasis 1992 22 58-65. 

Hidaka, K, Tada, S, Matsumoto, M, Ohmori, J, Tasaki, Y, Nomura, T, Usuda, S and Yamaguchi, T (1996) In vitro pharmacological profile of YM-43611, a novel D2-like receptor antagonist with high affinity and selectivity for dopamine D3 and D4 receptors. Brit. J. Pharmacol. 117 1625-1632. 

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