Mouse vas deferens assay

Following on from this they demonstrated that the aminoethyl side chain could also be replaced (see Table 6.22) [180], the most potent ligands bearing a naphthoyl moiety. In particular, the piperidinyl analogue (258) was found to have a high affinity in the binding assay and potency in the mouse vas deferens assay. 

With the availability of a viable synthesis of 14-aminocodeinone (13) and the closely related analogues 20a, 26 and 27, Reckitt and Colman in collaboration with Professor Kirby set about the synthesis of a whole range of 14-alkylamino-, 14-arylalkylamino- and 14-acylaminocodeinones and equivalent morphinones as well as the 7,8-dihydro analogues and the /V-cyclopropylmethyl equivalents. The synthesised compounds were listed in two patents, US 4,241,066 and US 4,241,067 [8,9]. Many of them were evaluated in a primary screen for MOR activity, in vitro in the mouse vas deferens assay and in vivo in rat antinociceptive assays (Tables 1 and 2). In the in vivo assays tail pressure was the nociceptive stimulus for agonist activity, whereas for morphine antagonism warm water (55 °C) was used with tail withdrawal as the end point. 

A quite good correlation was also found nl) between the potency of the peptides in the mouse vas deferens assay and the relative hydrophobicity of the peptides, no j 2, at the composition of an aqueous medium providing the capacity of the medium to participate in electrostatic interactions which amounts to 0.322 in terms of the parameter C 111). The correlation is described as1111 ... 

Endorphin Analogs - D-Ala, N-MeMet -enkephallnamide ( ) has been found to be a potent parenteral analgesic.59 it was 238 times as potent as normor-phlne in the mouse vas deferens assay, and four times as potent as morphine in the mouse hot plate assay (jump response) after subcutaneous administration. It is claimed that has relatively little respiratory depressant properties or tendency to cause tolerance or physical dependence. A series of Met -enkephalin analogs extended at the amino terminus with amino acid residues corresponding to 6-LPH have been described. Using the guinea-pig ileum-myenteric plexus assay, potency was found to decrease dramatically on further extension of the g-LPH 60-65 sequence... 

However, while the Indane analog shows considerably less activity in the guinea pig ileum and mouse vas deferens assays chan [Leu ]enkephalln, the tetralin analog is more active in the guinea pig ileum (p-receptor) assay and much less active in the mouse vas deferens (6-receptor) assay than [leu ]enkephalin. Implying an Increase of receptor specificity by this conformational restriction. The use of dehydro amino acids to Induce rigidity and increase hydrophoblclty of the enkephalins has resulted in the u-selective [AAla , Leu ]enkephalln and the 6-selective [D -Ala ,... 

These peptides were characterized in vitro and found to be powerful opioid agonists in the mouse vas deferens (MVD) and guinea pig ileum (GPI) assay. In vivo (rat tail-flick) they are only active when administered directly to the brain - a general limitation of simple linear peptides consisting of natural L-amino acids - but with less potency and shorter duration of action than morphine (Casy and Parfitt, 1986). 

Among the compounds in Table 3, compound 5 showed the highest antitussive activity however, it showed a markedly reduced 5 receptor antagonist activity in the mouse vas deferens (MVD) assay (Table 4). In the MVD assay, the Ke value indicated the potency of the test compound antagonist activity for each receptor type. Compound 5 showed a markedly high Ke value (low potency) for the 8 receptor compared with that of unmodified NTI [39]. Moreover, compound 5 showed a reduced selectivity for the 8 receptor over the p and k receptors. This suggested that the antitussive activity of compound 5 may be induced by its active metabolites (e.g., 3-OH analog). 

ND not determined Determined in mouse vas deferens bDetermined in mouse vas deferens vs normorphine Determined in rat tail pressure assay dDetermined in rat tail withdrawal vs morphine e53 times normorphine in guinea pig ileum... 

An assay that measures the ability of ligands to inhibit electrically evoked contractions of the mouse vas deferens. 

Previous experiments performed in vitro with receptor binding assay [46, 74] mouse vas deferens (MVD) and guinea-pig ileum (GPI) [72] showed a marked delta opioid receptor preference. 

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