8 - selective receptor agonist

Phenylephrine (90) is a selective receptor agonist (+)-niguldipine (91) is a selective antagonist for the receptor. Pra2osin (92) and 5-methylurapidil (93) are nonselective a -receptor antagonists. CEC can differentiate receptors from the other receptors. Pra2osin has low and high affinity for and receptors, respectively. 

Pharmacology Prostanoid selective receptor agonists are believed to reduce lOP by increasing the outflow of aqueous humor. 

Mechanism of Action An ophthalmic agent that is a prostanoid selective receptor agonist. Therapeutic Effect Reduces intraocular pressure (lOP) by reducing aqueous humor production. 

Hall H, Halldin C, Dijkkstra D, Wikstrom H, Wise LD, Pugsley TA, Sokoloff P, Pauli S, Farde L, Sedvall G (1996) Autoradiographic localisation of D3 dopamine receptor in human brain using the selective receptor agonist 3H PD 128907. Psychopharmacol 723 240-247. 

Phenylephrine (neo-synephrine, others) is a selective receptor agonist it activates receptors only at much higher concentrations. The drug causes marked arterial vasoconstriction during intravenous infusion. Phenylephrine also is used as a nasal decongestant and as a mydriatic in various nasal and ophthalmic formulations (see Chapter 63 for ophthalmic uses). 

Acetylcholine (ACh) was the first neurotransmitter to be characterised. It binds efficiently to both AChNR and AChMR despite the differences in the active sites of the receptors. The dissimilarity of the active site is good news with regards to the different responses elicited by the activation of the two receptors, as it makes possible the rational design of highly selective receptor agonists or antagonists. 

DOI (294) and a-methyl-5-HT (295) are selective 5-HT2 receptor agonists. Ketansetin (296) and ritansetin (297) are potent and selective 5-HT2 antagonists. SB 200646 (298) is an antagonist which has greater selectivity toward 5-HT2g and receptors compared to the 5-HT2 subtype. 

Fig. 2. Molecular modeling of dopamine D2 receptor agonists used to define the molecular conformation needed for selective high affinity binding.

Krogsgaard-Larsen and co-workers have protected the P-keto functionality as a ketal as a modification to the traditional conditions so attack of hydroxylamine is directed towards the ester. They prepared hydroxamic acid 10 from ester 9 then cyclized with sulfuric acid to isoxazole 11, in route to 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), a selective GABAa receptor agonist studied clinically for insomnia. 

The most probable mechanism for inverse agonism is the same one operable for positive agonism namely, selective receptor state affinity. However, unlike agonists that have a selectively higher affinity for the receptor active state (to induce G-protein activation and subsequent physiological response) inverse agonists have a selectively higher affinity for the inactive receptor state and thus uncouple already spontaneously coupled [RaG] species in the system. 

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