Neuropeptide Y receptors­inviting targets

RESEARCH & DEVELOPMENT

Targetting neuropeptide Y (NPY) receptors is likely to reap the greatest benefit in developing drugs that specifically affect the actions of this neurotransmitter, according to C1aes Wahlestedt and Donald Reis, from Cornell University Medical College, New York, US.

NPY is probably the most abundant neuropeptide currently known and at least 3 receptor types have been established. This opens the door to numerous therapeutic possibilities, including the following:

OPeripherally-acting Y I receptor antagonists. such as R-116 and PP-56 [Perstorp; phase II], could prove to be useful antihypertensives by acting against NPY-induced vasoconstriction. Such agents may have the potentially unique ability to inhibit pressor responses to stress-induced increases in sympathetic nerve activity.

OStimulation of food intake by NPY could be blocked by a centrally acting NPY antagonist. The feeding response may be mediated by an atypical hypothalamic receptor, which suggests that a highly specific drug for this action could be developed without affecting other NPY-mediated effects.

OCentrally-acting Y I agonists are likely to be potent anxiolytics. Several substituted analogues of NPY. such as [Pr034 ]NPY and [Leu31. Pro34 ]NPY. have demonstrated specific Y I agonist activity.

Wahlestedt C, Reis DJ . Neuropepride Y·related peptides and their receplOrs -are the receptors potential therapeutic drug targets" Annual Review of Pharmacology and Toxicology 33: 309·352. 1993 ><00,.,,88

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INPHARMA~15 May 1993