Detail of "71048-87-8"

Reference

Effects of fixed-interval duration on the development of tolerance to decreased responding by l-nantradol

Effects of fixed-interval duration on the development of tolerance to decreased responding by l-nantradol. Smith, James B. (Worcester Found. Exp. Biol., Shrewsbury, MA 01545, USA). Psychopharmacology (Berlin), 91(1), 127-30 (English) 1987. CODEN: PSCHDL. ISSN: 0033-3158. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Key pecking of pigeons was maintained under a chained schedule in which the 1st response after 2 h (fixed interval) was followed by the opportunity to obtain food after sequences of 30 responses (fixed ratio), and animals received acute injections of l-nantradol [71048-87-8] (0.001-0.1 mg/kg). Smallest doses were ineffective; largest doses decreased all responding; and intermediate doses decreased fixed-interval, but not fixed-ratio, responding. When animals subsequently received daily administration of 0.1 mg/kg l-nantradol prior to exptl. sessions, initially decreased fixed-interval responding did not recover during 21 sessions of l-nantradol administration, whereas fixed-ratio responding was demonstrated on several occasions by automatic advancement to the fixed-ratio component. When the schedule was changed so that the same total amt. of food was available after 10 shorter fixed intervals, fixed-interval responding resumed within a single session, and when the schedule was changed back so that all food was available only after 2 h had elapsed, fixed-interval responding diminished within a few sessions and virtually no responding occurred for 21 addnl. sessions. The behavioral effects of chronic l-nantradol depended on both the schedule and the parameter of reinforcement.

Cannabinoid inhibition of adenylate cyclase

Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes. Howlett, Allyn C.; Fleming, Richard M. (Sch. Med., St. Louis Univ., St. Louis, MO 63104, USA). Mol. Pharmacol., 26(3), 532-8 (English) 1984. CODEN: MOPMA3. ISSN: 0026-895X. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Adenylate cyclase [9012-42-4] in plasma membranes was inhibited by micromolar concns. of D8-tetrahydrocannabinol [5957-75-5] and D9-THC [1972-08-3] and by levonantradol [71048-87-8] and desacetyllevonantradol [80286-75-5]. This inhibition was noncompetitive for stimulation of the enzyme at the prostanoid receptor by PGE1 or prostacyclin, or at the peptide receptor by secretin or vasoactive intestinal peptide. Forskolin-activated adenylate cyclase was also inhibited by cannabimimetic agents. Inhibition by cannabinoid compds. was neither synergistic nor additive with muscarinic or a-adrenergic agents when each was present at maximal inhibitory concns. Cannabinoid inhibition was not blocked by atropine, yohimbine, or naloxone, suggesting that muscarinic, a2-adrenergic, and certain opiate receptors may not be required for the response. The inhibition of adenylate cyclase was specific for psychoactive cannabinoids, since cannabinol [521-35-7] and cannabidiol [13956-29-1] produced minimal or no response. Inhibition was also stereoselective, since dextronantradol [74430-97-0] did not produce the response. A biphasic log dose-response curve was obsd. for each of the cannabinoid drugs, such that reversal of the inhibition occurred at 3-10 mM. Possible mechanisms for the effects of cannabinoid drugs on adenylate cyclase activity are discussed.