D-Arg1, D-Trp7,9, Leu11-substance P (spantide) does not antagonize substance P-induced hyperexcitability of the nociceptive flexion withdrawal reflex in the rat.
The effect of D-Arg1, D-Trp7,9, Leu11-substance P (SP) (spantide), a putative SP antagonist, on SP-induced facilitation of the flexion reflex was examined. The drugs were injected intrathecally (i.t.) in decerebrate, spinalized, unanaesthetized rats. Substance P (10 ng) caused an increase in reflex magnitude for about 5 min. Spantide (10 ng and 100 ng) also caused a facilitation of the reflex that was similar to SP. Spantide (10 ng) plus SP (10 ng) also had a similar excitatory effect. One microgram of spantide totally blocked the flexion reflex, which could not be reversed by SP, L-glutamate, L-aspartate or naloxone. It is concluded that spantide does not have an antagonistic effect on SP-induced changes in spinal reflex excitability. Some of the effects of i.t. spantide observed in behavioural studies may be due to a non-specific spinal motor block. It is suggested that the flexion reflex in the decerebrate, spinalized rat is a useful physiological model in studies of the effects of algesic and analgesic drugs at spinal level.
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007278:Injections, Spinal; D009270:Naloxone / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D010812:Physical Stimulation; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects*; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D005971:Glutamates; D001224:Aspartic Acid; D013373:Substance P; D009270:Naloxone; D018698:Glutamic Acid; C038073:substance P, Arg(1)-Pro(2)-Trp(7),(9)-LeuNH(2)(11)-; C042867:spantide