Michael J Cumberbatch

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This study investigated whether the selective 5HT1F receptor agonist LY334370 has other possible antimigraine mechanisms in addition to the proposed inhibition of dural plasma extravasation. LY334370 (up to 10(-5) M) had no vasoconstrictor effects on human cerebral arteries in vitro. It had no effect (up to 10 mg kg-1, i.v.) on neurogenic vasodilation of(More)
The anti-emetic profile of the novel brain penetrant tachykinin NK1 receptor antagonist MK-0869 (L-754,030) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluor o)phenyl-4-(3-oxo-1,2,4-triazol-5-yl)methylmorpholine and its water soluble prodrug, L-758,298, has been examined against emesis induced by cisplatin in ferrets. In a 4 h observation(More)
Substance P receptor [neurokinin 1 (NK1] antagonists (SPAs) represent a novel mechanistic approach to antidepressant therapy with comparable clinical efficacy to selective serotonin reuptake inhibitors (SSRIs). Because SSRIs are thought to exert their therapeutic effects by enhancing central serotonergic function, we have examined whether SPAs regulate(More)
In vivo electrophysiological assays in anesthetized rats have been used to compare the effects of the 5HT1B/1D receptor agonist, naratriptan, on central trigeminal nociceptive processing from dural and cutaneous inputs with its effects on nociceptive processing in the spinal cord. Naratriptan inhibited responses of single trigeminal neurons, to noxious(More)
The relative roles of receptors for AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) in spinal nociceptive and non-nociceptive transmission were studied on dorsal horn wide dynamic range neurones in alpha-chloralose-anaesthetized spinalized rats. The effects of systemically administered competitive and non-competitive AMPA antagonists (the(More)
The importance of receptors for N-methyl-D-aspartate in synaptic plasticity and in triggering long-term pronociceptive changes is explained by their voltage-dependence. This suggests that their contribution to acute nociceptive responses would be determined both by the magnitude of synaptic input and by the level of background excitation. We have now(More)
The mechanism of action of conventional antidepressants (e.g. imipramine) has been linked to modulation of central monoamine systems. Substance P (NK1) receptor antagonists may have antidepressant and anxiolytic effects in patients with major depressive disorder and high anxiety but, unlike conventional antidepressants, are independent of activity at(More)
1. The effects of selective tachykinin (neurokinin, NK) NK1 and NK2 receptor antagonists have been examined on spinal neurones in alpha-chloralose anaesthetized, spinalized rats. They were tested for effects on responses both to excitatory amino acids (EAA) and to noxious heat stimuli. They were also tested for their ability to reverse the actions of(More)
1. The effects of intravenous administration of two alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonists were studied on responses of single neurones to iontophoretically applied excitatory amino acids. The tests were performed on spinal neurones in alpha-chloralose anaesthetized, spinalized rats. 2. Both the quinoxaline, NBQX (2-16(More)
In adult rats response latencies to innocuous mechanical stimuli were found to be reduced and, in electrophysiological studies, the receptive fields of dorsal horn neurones were enlarged 7-14 days after chronic constriction injury of the sciatic nerve. The NK1 receptor antagonist GR205171 at 3 mg kg(-1) blocked responses to NK1 agonist evoked activity and(More)