Assessment of 'active investigation' as a potential measure of female sexual incentive motivation in a preclinical non-contact rodent model: observations with apomorphine.

Clinical studies have suggested therapeutic potential for the non-selective dopamine receptor agonist apomorphine, in treating female sexual dysfunction. However, experimental data suggest apomorphine may inhibit sexual behaviour in female rats. The aims of this study were: evaluate an alternate behavioural endpoint in a conscious, non-contact model of sexual behaviour; and secondly investigate apomorphine in this model.

I. Slow oscillations in vaginal blood flow: alterations during sexual arousal in rodents and humans.

Purpose: This study investigated slow oscillatory rhythms in vaginal blood flow as a physiological marker of female sexual arousal in rodents, human healthy volunteers, and women with female sexual arousal disorder (FSAD).

Materials And Methods: Vaginal blood flow was measured in urethane-anesthetized rodents using laser Doppler flowmetry, while in humans, vaginal photoplethysmography was used. Acquired data were filtered for frequency analysis in the range of 0.

Effect of single point mutations of the human tachykinin NK1 receptor on antagonist affinity.

Molecular modelling and site-directed mutagenesis were used to identify eleven amino acid residues which may be involved in antagonist binding of the human tachykinin NK1 receptor. Recombinant receptors were expressed in mammalian cells using the Semliki Forest virus system. Wild type and mutant receptors showed similar expression levels in BHK and CHO cells, verified by metabolic labelling.

GR205171: a novel antagonist with high affinity for the tachykinin NK1 receptor, and potent broad-spectrum anti-emetic activity.

It has been demonstrated recently that antagonists of the tachykinin NK1 receptor, specifically CP-99,994 and GR203040, possess anti-emetic activity in a range of species. To optimise this activity, a series of analogues based around the structure of GR203040 have been synthesised and their affinity at the human tachykinin NK1 receptor determined. In addition, the potency of these analogues to inhibit emesis induced in the ferret by whole-body X-irradiation has been examined.

Temperature and agonist dependency of tachykinin NK1 receptor antagonist potencies in rat isolated superior cervical ganglion.

Using rat isolated superior cervical ganglion we have further characterised tachykinin NK1 receptors and investigated the possible existence of tachykinin NK1 receptor subtypes. At 37 degrees C, tachykinin NK1 receptor antagonists GR82334 ([D-Pro9[spiro-gamma- lactam]Leu10,Trp11]physalaemin-1(1-11)), CP-99,994 ((+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine) and (+/-)-RP67580 (7,7-diphenyl-2[1-imino-2(2-methoxy- phenyl)-ethyl]perhydroisoindol-4-one (3aR,7aR)) antagonised more potently depolarisation responses evoked by GR73632 (delta Ava]L-Pro9,N-MeLeu10]SP-(7-11)), septide ([pGlu6,Pro9]SP-(6-11)) and neurokinin A than those evoked by substance P, substance P O-methyl ester and [Sar9,Met(O2)11]substance P. GR73632 and substance P O-methyl ester evoked depolarisation responses of similar magnitude, unaffected by addition of tetrodotoxin, but which cross-desensitised.