Analgesic and other effects of the <i>d</i>‐ and <i>l</i>‐isomers of pentazocine

Forrest, William H.; Beer, E. George; Bellville, J. Weldon; Ciliberti, Benjamin J.; Miller, Elliott V.; Paddock, Richard

doi:10.1002/cpt1969104468

Cited by 28 publications

(7 citation statements)

References 2 publications

(2 reference statements)

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“…(Lasagna and Beecher, 1954), this did not give rise to corresponding hypotheses, since at that time there was no known link between opiate effects and brain neuron systems. Later a similar subjective response has been reported to other partial antagonists like pentazocine (Forrest et at., 1969;Jasinski, Martin and Hoeldtke, 1970), cyclazocine (Lasagna, Kornfeld and Pearson, 1964), tevaltorphan (Swerdlow, 1958) and cyclorphan (Lasagna, 1965). Interestingly this psychotomimetic action can be antagonized by the pure morphine antagonist naloxone (]asinski, Martin and Sapira, 1968).…”

Section: Discussionmentioning

confidence: 55%

Naloxone-induced reversal of schizophrenic hallucinations

Gunne¹,

Lindström²,

Terenius³

1977

J. Neural Transmission

256

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Section: Discussionmentioning

confidence: 55%

Naloxone-induced reversal of schizophrenic hallucinations

Gunne¹,

Lindström²,

Terenius³

1977

J. Neural Transmission

256

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“…In contrast to the effect of NANM on PPI in mice, most of the available evidence indicates that benzomorphans induce hallucinations by activating KOR. The hallucinogenic effects of pentazocine are attributable to the (−)-stereoisomer (Forrest et al, 1969), which has high affinity for the κ 1 KOR subtype (Chien and Pasternak, 1995) and low affinity for the PCP binding site (Carroll et al, 1992). Similarly, naloxone blocks the dysphoria induced by cyclazocine (Jasinski et al, 1968) and the hallucinogenic effects of (±)-MR 2033 and (−)-MR 2033 (Pfeiffer et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

“…Those findings are notable because naloxone does not interact with σ 1 receptors at concentrations up to 100 μM (Su, 1982; Tam, 1983, 1985; Tam and Cook, 1984). A study comparing the effects of (+)- and (−)-pentazocine reported that the psychotomimetic side effects of pentazocine are mediated by the (–)-stereoisomer (Forrest et al, 1969). This contrasts with the preference of the σ 1 receptor for (+)-benzomorphans; (+)-pentazocine has approximately 25-fold higher affinity than (–)-pentazocine for σ 1 (De Costa et al, 1989; Carroll et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

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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“…The confusion from the contradictory data obtained in earlier experiments could have resulted from the fact that it was the racemic form of pentazocine, which was initially used in some of the experiments which generated psychomimetic symptoms. Later, further studies focused on determining which isomer was responsible for the adverse side effects of pentazocine (Forrest et al, 1969). It was found that the psychomimetic side effects were generated by the L-isomer, although the d-pentazocine produced, to a lesser extent, some degree of anxiety (Bellville and Forrest, 1968).…”

Section: Discussionmentioning

confidence: 99%