Biomedical subjects

T L Goode

Publications and source records attributed to T L Goode.

5 recordsLinked to original sources

PubMed1997

An examination of the relationship between mu-opioid antinociceptive efficacy and G-protein coupling using pertussis and cholera toxins.

The hypothesis that mu-opioid agonists having low antinociceptive efficacy might be more susceptible to interference with G-protein coupling than mu-opioid agonists having higher antinociceptive efficacy was tested. Supraspinal antinociceptive efficacy for the three mu-opioid agonists morphine, [D-Ala2, NMePhe4, Gly5-ol]-enkephalin (DAMGO) and sufentanil in the mouse 55 degrees C warm-water tail-flick test was evaluated 18-24 h after intracerebroventricular (i.c.v.) administration of beta-funaltrexamine (beta-FNA). The beta-FNA pretreatment (0.2-2.0 nmol) attenuated antinociception in the order morphine > DAMGO > sufentanil, consistent with previous reports of their relative antinociceptive efficacy. The association of efficacy with G-protein coupling was then assessed by determining sensitivity to i.c.v. (0.1-3.0 micrograms) pertussis toxin (PTX) or cholera toxin (CTX). The effect of PTX on equiantinociceptive doses was in the inverse order of agonist efficacy. CTX augmented sufentanil-induced antinociception. Morphine- and DAMGO-induced antinociception were unaffected by CTX. These data suggest that: (i) highly efficacious mu agonists (viz., sufentanil) couple more efficiently to PTX-sensitive inhibitory Gi-proteins than do agonists of lower efficacy (viz., morphine, DAMGO) and (ii) highly efficacious mu agonists have greater capacity to utilize CTX-sensitive stimulatory Gs-proteins than do mu-agonists with lower efficacy.

Analgesics↗

PubMed1996

A Gi2alpha antisense oligonucleotide differentiates morphine antinociception, constipation and acute dependence in mice.

In the same mice in which the intracerebroventricular (i.c.v.) administration of antisense oligodeoxyribonucleotide (oligo) directed against the Gi2alpha (but not Gi1alpha, Gi3alpha or G(s)alpha) G-protein subunits attenuated i.c.v. morphine-induced antinociception in the tail-flick test, none of the oligos altered naloxone-precipitated jumping (acute dependence). Likewise, none of the oligos significantly altered morphine-induced constipation. Hence, i.c.v. morphine-induced antinociception might be preferentially mediated via transduction pathway(s) different from constipation or acute dependence, offering novel opportunities for drug discovery.

Analgesics, Opioid↗

PubMed1989

Central administration of p-octopamine to mice: assessment of antinociception.

Administration of p-octopamine by intracerebroventricular (i.c.v.) or intrathecal (i.t.) routes, but not orally, produced antinociception in the acetylcholine-induced abdominal constriction test (ED50 = 24.8 and 3.6 micrograms, respectively). Likewise, i.c.v. and i.t., but not peripheral (up to 200 mg/kg s.c.), administration increased latency in the 48 degrees C hot-plate test (ED50 = 11.5 micrograms i.c.v. and 0.2 micrograms i.t.). These actions were relatively long-lasting and not blocked by naloxone. Antinociception following i.c.v. administration was abolished in reserpinized mice or by pretreatment with i.t. phentolamine (2 micrograms). These results suggest a moderate antinociceptive action of p-octopamine involving non-opioid, reserpine-sensitive, central pathways.

Analgesics↗

PubMed1987

Evidence that reciprocal hindlimb scratching elicited in mice by intrathecal administration of muscarinic agonists is mediated through M1 type receptors.

Intrathecal (IT) administration of pilocarpine to mice produces a vigorous and dose-related reciprocal hindlimb scratching (RHS) response (ED50 = 0.6 microgram) that is potently blocked by simultaneous IT administration of atropine (ID50 = 0.002 microgram). We now report that RHS is (1) also elicited by the more selective M1 agonist McN-A-343-11 (ED50 = 11.6 micrograms), (2) blocked by the selective M1 antagonist pirenzepine (ID50 = 0.001 microgram), and (3) is not blocked by the selective M2 antagonist AF-DX 116 BS at a dose up to 100 times the ID50 dose of pirenzepine. These results extend our earlier findings and suggest that the RHS elicited in mice by IT injection of muscarinic agonists is mediated through pirenzepine-sensitive (presumably M1) receptors and that RHS may be a convenient in vivo centrally mediated M1 endpoint.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

PubMed1987

Pilocarpine-induced reciprocal hindlimb scratching in mice.

Intrathecal (IT) administration of pilocarpine (0.25-2.0 micrograms) to mice produced a vigorous and dose-related reciprocal hindlimb scratching response that lasted for 10-15 minutes. Neither the intracerebroventricular administration of pilocarpine at up to 10 times the intrathecal ED90 dose nor the subcutaneous administration of 10 mg/kg pilocarpine caused as robust an effect as IT administration. The reciprocal hindlimb scratching produced by the ED90 dose of pilocarpine (2 micrograms, IT) was antagonized in a dose-related manner by simultaneous IT administration of atropine (ID50 = 0.002 micrograms), methysergide (ID50 = 1.89 micrograms), the substance P antagonist [D-Pro2,D-Trp7,9]-SP (ID50 = 4.94 micrograms), and the putative neurokinin B antagonist [D-Pro2,D-Trp6,8,Nle10]-NK (ID50 = 3.33 micrograms), but not by yohimbine (5 micrograms), phentolamine (2 micrograms), or naloxone (2.5 micrograms). These results suggest that pilocarpine-induced reciprocal hindlimb scratching is mediated spinally, that the effect is produced by an action of pilocarpine on muscarinic receptors in the spinal cord, and that neurokinin, and perhaps 5-HT, mechanisms might also be involved.

Animals↗