Straub tail effect

The extraordinary antinociceptive potency of the unknown compound was determined in a mouse model of acute nociception, the hot plate test. Despite the Straub-tail effect observed earlier, the antinociceptive effect of the compound could not be not antagonized with the p-opioid receptor antagonist naloxone but with the nAChR antagonist mecamylamine, so the unknown compound was deduced to be a potent nicotinic analgesic (Spande et al., 1992 Qian et al., 1993 Badio and Daly, 1994 Sullivan and Bannon, 1996). 

The acute CNS effects of MDMA administration are mediated by the release of monoamine transmitters, with the subsequent activation of presynaptic and postsynaptic receptor sites.40 As specific examples in rats, MDMA suppresses 5-HT cell firing, evokes neuroendocrine secretion, and stimulates locomotor activity. MDMA-induced suppression of 5-HT cell firing in the dorsal and median raphe involves activation of presynaptic 5-HT1A autoreceptors by endogenous 5-HT.4142 Neuroendocrine effects of MDMA include secretion of prolactin from the anterior pituitary and corticosterone from the adrenal glands 43 Evidence supports the notion that these MDMA-induced hormonal effects are mediated via postsynaptic 5-HT2 receptors in the hypothalamus, which are activated by released 5-HT. MDMA elicits a unique profile of locomotor effects characterized by forward locomotion and elements of the 5-HT behavioral syndrome such as flattened body posture, Straub tail, and forepaw treading.44 6 The complex motor effects of MDMA are dependent on monoamine release followed by activation of multiple postsynaptic 5-HT and DA receptor subtypes in the brain,47 but the precise role of specific receptor subtypes is still under investigation. 

In the above discussion on the mu/kappa receptor selectivity of the U-50488 (5) series, the steric properties of the tertiary amine and the distance between the amide and the aromatic ring were cited as important factors. This has been exploited by the Upjohn company to give the arylformamide-dimethyl-amine derivative (52) which is an analgesic in the mouse tail flick test (ED50 = 0.2 mg/kg s.c.) and causes mu-opioid like side-effects such as Straub tail, arched back and increased locomotor activity [81]. These behavioural effects and the association constant for the morphine receptor of compound... 

When the terminal anilino moiety of the 4-substituent of 30 is replaced by methylaminocyclohexane, a compound as active as morphine results (ED50 3.2 mg/kg) the dextro antipode (ED50 42 mg/kg) is distinctly less active than the racemic mixture, but the levo form (ED50 3.8 mg/kg) does not show the expected doubling of potency. The more potent members of the group effectively displace [3H]naloxone from rat brain membranes provided NaCl is absent, while theN-propyl analog of 30 (a typical member) produced mydriasis accompanied by a Straub tail response and CNS depressant effects... 

Another approach to the separation of antldlarrheal from narcotic analgesic activity was the conparison of Straub-tail vs. constipating effects.35 ci-750 (XII), selected for evaluati[Pg.14]

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