Narcotic Antagonists as Analgesics

Archer, Sydney; Albertson, Noel F.; Harris, Louis S.; Pierson, Anne K.; Bird, Joseph G.; Keats, Arthur S.; Telford, Jane; Papadopoulos, Christos

doi:10.1126/science.137.3529.541

Cited by 64 publications

(12 citation statements)

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“…Postoperative patients treated with N -allylnormetazocine (NANM, SKF-10,047) experienced profound hallucinogenic and dysphoric effects (Keats and Telford, 1964). Similar effects are induced by other benzomorphans, including pentazocine and cyclazocine (Archer et al, 1962; Lasagna et al, 1964; Haertzen, 1970; Beaver and Feise, 1977; Coursey, 1978; Kumor et al, 1986). …”

Section: Introductionmentioning

confidence: 84%

Effects of the psychotomimetic benzomorphan N -allylnormetazocine (SKF 10,047) on prepulse inhibition of startle in mice

Halberstadt

Hyun

Ruderman

et al. 2016

Pharmacology Biochemistry and Behavior

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N-allylnormetazocine (NANM; SKF 10,047) is a benzomorphan opioid that produces psychotomimetic effects. (+)-NANM is the prototypical agonist for the sigma-1 (σ1) receptor, and there is a widespread belief that the hallucinogenic effects of NANM and other benzomorphan derivatives are mediated by interactions with σ1 sites. However, NANM is also an agonist at the κ opioid receptor (KOR) and binds to the PCP site located within the channel pore of the NMDA receptor, interactions that could potentially contribute to the effects of NANM. NMDA receptor antagonists such as phencyclidine (PCP) and ketamine are known to disrupt prepulse inhibition (PPI) of acoustic startle, a measure of sensorimotor gating, in rodents. We recently found that racemic NANM disrupts PPI in rats, but it is not clear whether the effect is mediated by blockade of the NMDA receptor, or alternatively whether interactions with KOR and σ1 receptors are involved. The present studies examined whether NANM and its stereoisomers alter PPI in C57BL/6J mice, and tested whether the effects on PPI are mediated by KOR or σ1 receptors. Racemic NANM produced a dose-dependent disruption of PPI (3–30 mg/kg SC). (+)-NANM also disrupted PPI, whereas (−)-NANM was ineffective. Pretreatment with the selective KOR antagonist nor-binaltorphimine (10 mg/kg SC) or the selective σ1 antagonist NE-100 (1 mg/kg IP) failed to attenuate the reduction in PPI produced by racemic NANM. We also found that the selective KOR agonist (−)-U-50,488H (10–40 mg/kg SC) had no effect on PPI. These findings confirm that NANM reduces sensorimotor gating in rodents, and indicate that the effect is mediated by interactions with the PCP receptor and not by activation of KOR or σ1 receptors. This observation is consistent with evidence indicating that the σ1 receptor is not linked to hallucinogenic or psychotomimetic effects.

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Section: Introductionmentioning

confidence: 84%

Effects of the psychotomimetic benzomorphan N -allylnormetazocine (SKF 10,047) on prepulse inhibition of startle in mice

Halberstadt

Hyun

Ruderman

et al. 2016

Pharmacology Biochemistry and Behavior

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“…7). Thus, it was revealed that a dose of s.c. pentazocine not more than 20 (20)(21)(22)(23)(24)(25).…”

Section: Methodsmentioning

confidence: 99%

Biphasic action of pentazocine in morphine-dependent rats.

et al. 1982

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Abstract-The characteristic actions of pentazocine in morphine-dependent rats were investigated by a drug-admixed food (DAF) method. Pentazocine did not cause evident withdrawal signs when stopped after a continuous administration for 2 months at 3 different dose levels. A state of physical dependency on morphine was produced in rats by feeding them for 3 weeks with food that contained different levels of morphine. Animals exhibiting a moderate degree of morphine-withdrawal signs (17-18 hr after with drawal) received a s.c. cross-administration with pentazocine at 0, 5, 10, 20, 40, 80, and 150 mg/kg. This drug at 20 mg/kg proved most supressive of morphine-withdrawal signs, being about 1 /4 as potent as codeine. In a dose range from 20 to 40 mg/kg, the action of pentazocine on the with drawal signs was reversed, that is, doses not less than 40 mg/kg exerted a dose-related antagonistic action in all the 3 levels of morphine dependent rats. The challenge with levallorphan (2 mg/kg, s.c.) during the chronic application of pentazocine revealed slight withdrawal signs. These findings show that pentazocine has biphasic action on morphine dependence and suggests that this type of drug must have different properties from morphine type drugs.

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“…Pen tazocine, (2a,6a,ll R* ) -( f )-1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(3-methyl-2-butenyl) -2,6-methano-3-benzazocin-8-01' (Ia), is a member of the benzomorphan series of compounds (1). Pentazocine is a potent, analgesic and a weak narcotic antagonist, possessing little dependence potential (2).…”

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confidence: 99%