新藥研制方略

Drug development strategies

Several strategies have been used in the development of new drugs. Over the years all have had success but no single approach has been consistently successful.

新藥研制方略

近年來，幾種方略被用于新藥的研發(fā)，他們均取得了成功，但沒有哪種方法是長盛不衰的。

Serendipity, luck and intuition.

偶然發(fā)現(xiàn)、運氣及直覺

This approach has been applied less frequently in recent years. The discovery of penicillin by Fleming was in this category.

此法近年來應(yīng)用較少。弗萊明發(fā)明青霉素屬于此類

Molecular roulette.

Random chemical synthesis of new structures and pharmacological screening. This approach is wasteful and depends on the availability of sensitive animal or in-vitro models of human disease, which often do not exist.

分子輪盤賭。

對新結(jié)構(gòu)式及藥理篩選的隨機化學(xué)合成。此法耗費巨大，且有賴于得到往往很難得到的可利用的敏感型動物或人類疾病的體外模型。

Minor structural changes in existing agents.

Occasionally this leads to compounds of greater efficacy and rarely to drugs with novel actions detected in pharmacological screening or clinical practice.

對現(xiàn)有藥物分子結(jié)構(gòu)的修飾。此法偶爾可產(chǎn)生功效更高的化合物，但罕有可能產(chǎn)生藥理篩選和臨床實踐中被檢測出具有全新功效的藥物。

Programmed basic research with synthesis of specific chemical.

Intellectually this approach is the most satisfying. There have been spectacular results, e.g. levodopa and dopamine agonists in the treatment of Parkinsonism; beta-receptor blockers for angina; histamine (H2) antagonists in peptic ulcer disease; converting enzyme inhibitors in hypertension. However, this approach is expensive and there is no guarantee of success.

針對特定化學(xué)物質(zhì)合成而制定的有計劃的基礎(chǔ)研究。

從研究的角度看，這種方法最為令人滿意，至今已取得顯著成功，例如:治療帕金森神經(jīng)功能障礙所用的左旋多巴及多巴胺;治療心絞痛的腎上腺素受體阻滯劑;消化性潰瘍病使用的組胺拮抗藥;用于高血壓的轉(zhuǎn)換酶抑制劑。不過，此法耗費巨大，且前景莫測。

Clinical observation of drug action in practice.

This is the traditional means of drug assessment. New applications arise from measurement of drug action in man in disease states. The antihypertensive effects of thiazide diuretics and beta-blockers were not predicted from animal screening tests. They were only identified after the drugs were available and were being used in practice.

使用中藥物作用的臨床觀察。

這是藥物評估的傳統(tǒng)方法。通過對人體處于疾患狀態(tài)中藥物作用的評估，人們發(fā)現(xiàn)其有新的應(yīng)用價值。噻嗪類利尿劑的抗高血壓作用在動物檢涵試驗中并沒發(fā)現(xiàn)而是在這些藥物投放市場并被實際應(yīng)用后，其上述作用才被發(fā)現(xiàn)。

醫(yī)學(xué)英語