Disease relevance of Lilly 78335

• When rats were pretreated with 2,3-dichloro-alpha-methylbenzylamine, an inhibitor of phenylethanolamine N-methyltransferase, the enzyme catalyzing the formation of epinephrine from norepinephrine, 80 mg/kg i.p. before decapitation, the l-propranolol-induced decrease was abolished completely.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

Psychiatry related information on Lilly 78335

• The centrally active inhibitors of phenylethanolamine-N-methyltransferase (PNMT), LY 78335 and LY 134046, were investigated both alone and in combination with ethanol (2 g/kg) in a holeboard test of directed exploration and locomotor activity [2].

High impact information on Lilly 78335

• Selective inhibitors of epinephrine synthesis, SKF 64139 and 2,3-dichloro-alpha-methylbenzylamine (DCMB), significantly reduced (P less than 0.01) the ACTH response to 0.05 mg/kg body wt nicotine iv, without affecting median eminence CRF content [3].
• Selective inhibitors of epinephrine synthesis, SKF 64139 or 2,3-dichloro-alpha-methylbenzylamine, administered on the same schedule, reduced (P less than .01) the prolactin response to N without altering responsiveness to the dopamine receptor antagonist, domperidone.(ABSTRACT TRUNCATED AT 250 WORDS)[4]
• Intraperitoneal injections of the phenylethanolamine N-methyltransferase inhibitors 2-cyclohexyl-2-hydroxyethylamine, 1-aminomethylcycloundecanol, 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline and 2,3-dichloro-alpha-methylbenzylamine all lowered blood pressures in spontaneously hypertensive rats [5].
• These studies show that (1) E-containing neurons in the hypothalamus may play an important role in the preovulatory LH release; (2) LY 78335 may exert inhibitory effects on preovulatory LH release, in part, by blocking alpha 1-adrenoreceptors, and (3) participation of NE and DA, if any, in evoking preovulatory LH release remains to be ascertained [6].
• Prior suppression of E levels selectively with LY 78335 blocked the preovulatory LH surge and ovulation [6].

Biological context of Lilly 78335

• Inhibitors of phenylethanolamine-N-methyltransferase. 2. Comparison of nonaromatic analogs of phenylethanolamines, 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline (SKF-64139) and 2,3-dichloro-alpha-methylbenzylamine: effects on rat brain and adrenal catecholamine content and blood pressure [5].

Gene context of Lilly 78335

• 4. Rat liver TMT activity was maximally inhibited by 57 +/- 6% by 1000 microM 2,3-dichloro-alpha-methylbenzylamine (DCMB), whereas human TMT was completely inhibited [7].

References