On the mode of action and biochemical properties of anti-inflammatory drugs-II.

The inhibition of prostaglandin (PG) synthetase by nonsteroidal anti-inflammatory drugs (NSAID) is not well understood. Co-factors (glutathione and hydroquinone) are needed for maximum enzymatic activity in vitro, and we suggest that NSAID might inhibit PG synthetase partly by interfering with co-factor induced stimulation of the enzyme. This hypothesis was tested by: A) Examining the effect of glutathione, noradrenaline and hydroquinone on bull seminal vesicle (BSV) PG synthetase in vitro. The stimulatory effects were concentration-dependent. B) Three structurally distinct NSAID, indomethacin, aspirin and paracetamol, inhibited the stimulation by each co-factor in a concentration-related manner. Drug effectiveness also depended on the concentration of co-factor.