Clinical profile

Desipramine [50-47-5] (35) and nortriptyline [72-69-5] (36) are demethylated derivatives and principal metaboHtes of (32) and (33), respectively. Both compounds possess less sedative and stronger psychomotor effects than the tertiary amine counterparts, probably because tricycHcs containing secondary amine groups generally show greater selectivity for inhibiting the reuptake of norepinephrine compared with the reuptake of serotonin. Protriptyline [438-60-8] (37), a stmctural isomer of nortriptyline, is another important secondary amine that displays a similar clinical profile. 

FIGURE 8.20 Drugs as subsets of clinical profiles. While burimamide, cimetidine, and metiamide are all active histamine H2 antagonists with ulcer healing activity burimamide lacks a suitable toxicity and pharmacokinetic profile and cimetidine is adequately absorbed but still toxic. Only metiamide fulfills the requirements of a clinically useful drug. 

The impact of immunomodulatory protein therapeutics on diseases having unmet medical need has already proven remarkable. These new treatments have been credited with a favorable clinical profile from slowing the disease progression to outright cures. Although the cost of these advanced medicines may be offset by the enormous improvement in the quality of life of numerous patients, we must remain vigilant throughout their clinical development. 

The early empirical structure-activity relationships promoted discovery of second-generation anticancer drugs such as complexes 2 and 3. However, analogs of these drugs usually display similar clinical profiles to the parent drugs. Therefore new classes of platinum complexes are required with distinct properties. 

Sophisticated ADME/Tox models and empirical rules derived from increasing amounts of pre-clinical profiling and safety pharmacology data... 

Although fosfluconazole is some 25-fold less active than fluconazole in vitro, it is rapidly hydrolyzed by phosphatases in vivo and has similar efficacy in animal models and in patients, where it is 97% bioavailable (Hegde and Schmidt, 2005). The prodrug has a half-life of 2.3 h in patients, and the vast majority of the dose is excreted as fluconazole. Consequently, fosfluconazole has a similar clinical profile to that of fluconazole. 

Dopamine is an intermediate product in the biosynthesis of noradrenaline. Furthermore it is an active transmitter by itself in basal ganglia (caudate nucleus), the nucleus accumbens, the olfactory tubercle, the central nucleus of the amygdala, the median eminence and some areas in the frontal cortex. It is functionally important, for example in the extra-pyramidal system and the central regulation of emesis. In the periphery specific dopamine receptors (Di-receptors) can be found in the upper gastrointestinal tract, in which a reduction of motility is mediated, and on vascular smooth muscle cells of splanchnic and renal arteries. Beside its effect on specific D-receptors, dopamine activates, at higher concentrations, a- and -adrenoceptors as well. Since its clinical profile is different from adrenaline and noradrenaline there are particular indications for dopamine, like situations of circulatory shock with a reduced kidney perfusion. Dopamine can dose-dependently induce nausea, vomiting, tachyarrhythmia and peripheral vasoconstriction. Dopamine can worsen cardiac ischaemia. 

Reddy, Y.C., Girimaji, S., and Srinath, S. (1997) Clinical profile of mania in children and adolescents from the Indian subcontinent. Can ] Psychiatry 42 841-846. 

Liebermann, J.A. and Safferman, A.Z. (1992) Clinical profile of clozapine adverse reactions and agranulocytosis. Psychiat Q 63 51-70. 

Harto N, Branconnier RJ Clinical profile of gepirone, a nonbenzodiazepine anxiolytic. Psychopharmacol Bull 24 154-160, 1988... 

Pharmacodynamics, antipsychotics also differ in their pharmacodynamics, i.e. their pharmacological and clinical profiles of action. A rough distinction is made between highly sedative, hypnotic antipsychotics (e.g. clopenthixol, levomepromazine) and other products with weaker initial sedative action (e.g. fluphenazine and haloperidol). Sedative antipsychotics are prescribed for states of major unrest, often combined with insomnia, whereas the less sedative antipsychotics are preferred for patients suffering from delusions and hallucinations but in whom heavy sedation during daytime is undesirable. 

Reports are on hand relating to more recent antidepressants such as bupropion, citalopram (Fairweather ei ul., 1997), fluoxetine (Gelfin et ul.. 1998). moclobemide (Dingemanse et ul., 1998) and paroxetine (Brauer et ul.. 1995). These products, in agreement with their clinical profiles, produce fewer subjective effects and generally less sedation in healthy subjects than the older... 

However, since the inception of these experiments the clinical profile of lapatinib has also become clearer. In the pivotal phase 111 study of lapatinib in combination with capecitabine (15), rates of diarrhea and skin rash were higher on the combination arm... 

Etidocaine is a long-acting amide LA with a physicochemical and clinical profile similar to bupivacaine. Toxic side-effects occur at total doses of 300 to 400 mg. It is clinically available in combination with the vasoconstrictor adrenaline. 

FIGURE 11 — 15. Haloperidol pharmacological icon. Haloperidol is different from many of the other conventional antipsychotic drugs in that it is more potent it also lacks potent antimuscarinic and antihistaminic binding activities. Otherwise, its clinical profile is highly conventional. 

Knopp RH. Clinical profiles of plain versus sustained-release niacin (Niaspan) and the physiologic rationale for nighttime dosing. Am J Cardiol 1998 82(12A) 24U-28U ... 

Hajos M, Fleishaker JC, Filipiak-Reisner JK, et al. The selective norepinephrine reuptake inhibitor antidepressant reboxetine pharmacological and clinical profile. CNS Drug Rev. 2004 10 23-44. 

Benagiano G, Primiero FM, Farris M. Clinical profile of contraceptive progestins. EurJ Contracept Reprod Health Care. 2004 9 182-193. 

Antilla SA, Leinonen EV (2001) A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev 7 249-264... 

Buckley PF (1999) New antipsychotic agents emerging clinical profiles. J Clin Psychiatry 60 Suppl 1 12-17. 

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