The tetrahydrobiopterin pathway and pain.

Novel approaches for treating chronic pain are required to address a widely recognized, yet largely underserved and unmet, clinical need. The recently discovered link between tetrahydrobiopterin (BH4) synthesis and pain in preclinical models and humans provides a promising new approach for treating neuropathic and other forms of chronic pain. The rate-limiting enzyme in BH4 synthesis, guanosine triphosphate cyclohydrolase 1 (GCH1), and sepiapterin reductase (SPR) are both promising drug targets based on initial active-site characterization of the SARs of these two enzymes.

Animal models in urological disease and sexual dysfunction.

There are several conditions associated with dysfunction of the lower urinary tract or which result in a reduction in the ability to engage in satisfactory sexual function and result in significant bother to sufferers, partners and/or carers. This review describes some of the animal models that may be used to discover safe and effective medicines with which to treat them. While alpha adrenoceptor antagonists and 5-alpha-reductase inhibitors deliver improvement in symptom relief in benign prostatic hyperplasia sufferers, the availability of efficacious and well-tolerated medicines to treat incontinence is less well served.

An investigation of the effects of zaprinast, a PDE inhibitor, on the nitrergic control of the urethra in anaesthetized female rats.

1. The effects of L-NAME and zaprinast were investigated (i.v.