Methods of treating pain and other conditions

A process for treating elevated intraocular pressure in a mammal, comprising administering to said mammal a pharmaceutical composition containing a therapeutically effective dose of selective agonist of an α2B adrenoceptor subtype or α2B/α2C adrenoceptor subtype(s), said selective agonist having a structure selected from the group consisting of compounds having the formula

• wherein the dotted lines represent optional double bonds;
• R is H or lower alkyl;
• X is S or C(H)R1, wherein R1 is H or lower alkyl or R1 is absent when X is S or when the bond between X and the ring represented by
• is a double bond;
• Y is O, N, S, (CR1x)y, wherein y is an integer of from 1 to 3, —CH═CH— or —Y1CH2—, wherein Y1 is O, N or S;
• x is an integer of 1 or 2, wherein x is 1 when R2, R3 or R4 is bound to an unsaturated carbon atom and x is 2 when R2, R3 or R4 is bonded to a saturated carbon atom;
• R2 is H, lower alkyl, halogen, hydroxy, lower alkoxy, or oxo;
• R3 and R4 are, each, H, lower alkyl, hydroxy, lower alkoxy, or phenyl or, together, are —(C(R2)x)z—;
• —Y1(C(R2)x)z′—;
• —Y1(C(R2)x)y Y1—;
• —(C(R2)x)—Y1—(C(R2)x)—;
• —(C(R2)x)—Y1—(C(R2)x)—(C(R2)x)— and —Y1—(C(R2)x)—Y1—(C(R2)x)— wherein z is an integer of from 3 to 5, z′ is an integer of from 2 to 4 and x and y are as defined above, and further either end of each of these divalent moieties optionally attach at either R3 or R4 to form the condensed ring structure
• and the ring thus formed is totally unsaturated, partially unsaturated, or totally saturated provided that a ring carbon has no more than 4 valences, nitrogen no more than three and O and S have no more than two;
• or
• wherein W is a bicyclic radical selected from the group consisting of
• wherein R5, R6, R7 and R8 are selected from the group consisting of H and lower alkyl provided that at least one of R5 and R6 or R6 and R7 are OC(R9)C(R9)N(R) to form a condensed ring with
• wherein R9 is H, lower alkyl or oxo and
• wherein R10 is H, lower alkyl, phenyl or lower alkyl substituted phenyl, and Z is O or NH.

A process for administering to a mammal a pharmaceutical composition comprising a therapeutically effective dose of a compound to treat or prevent a pathological condition selected from the group consisting of muscle spasticity;

• pain;
• neurodegenerative diseases, spinal ischemia and stroke;
• memory and cognition deficits;
• psychoses, anxiety and depression;
• hypertension;
• congestive heart failure;
• cardiac ischemia and nasal congestion, wherein said compound has adrenergic activity and is a selective agonist of the α2B or α2B/α2C adrenoceptor receptor subtype(s), said selective agonist having a structure selected from the group consisting of compounds having the formula
• wherein the dotted lines represent optional double bonds;
• R is H or lower alkyl;
• X is S or C(H)R1, wherein R1 is H or lower alkyl or R1 is absent when X is S or when the bond between X and the ring represented by
• is a double bond;
• Y is O, N, S, (CR1x)y, wherein y is an integer of from 1 to 3, —CH═CH— or —Y1CH2—, wherein Y1 is O, N or S;
• x is an integer of 1 or 2, wherein x is 1 when R2, R3 or R4 is bound to an unsaturated carbon atom and x is 2 when R2, R3 or R4 is bonded to a saturated carbon atom;
• R2 is H, lower alkyl, halogen, hydroxy or lower alkoxy, or oxo;
• R3 and R4 are, each, H, lower alkyl, hydroxy, lower alkoxy, or phenyl or, together, are —(C(R2)x)z—;
• —Y1(C(R2)x)z′—;
• —Y1(C(R2)x)y Y1—;
• —(C(R2)x)—Y1—(C(R2)x)—;
• —(C(R2)x)—Y1—(C(R2)x)—(C(R2)x)— and —Y1—(C(R2)x)—Y1—(C(R2)x)— wherein z is an integer of from 3 to 5, z′ is an integer of from 2 to 4 and x and y are as defined above, and further either end of each of these divalent moieties optionally attach at either R3 or R4 to form the condensed ring structure
• and the ring thus formed is totally unsaturated, partially unsaturated, or totally saturated provided that a ring carbon has no more than 4 valences, nitrogen no more than three and O and S have no more than two;
• or
• wherein W is a bicyclic radical selected from the group consisting of
• wherein R5, R6, R7 and R8 are selected from the group consisting of H and lower alkyl provided that at least one of R5 and R6 or R6 and R7 are OC(R9)C(R9)N(R) to form a condensed ring with
• wherein R9 is H, lower alkyl or oxo and
• wherein R10 is H, lower alkyl, phenyl or lower alkyl substituted phenyl, and Z is O or NH.

A process for administering to a host mammal a pharmaceutical composition containing an effective dose of an active compound having adrenergic activity, said active compound having a structure selected from the group consisting of compounds having the formula

• wherein the dotted lines represent optional double bonds;
• R is H or lower alkyl;
• X is S or C(H)R1, wherein R1 is H or lower alkyl or R1 is absent when X is S or when the bond between X and the ring represented by
• is a double bond;
• Y is O, N, S, (CR1x)y, wherein y is an integer of from 1 to 3, —CH═CH— or —Y1CH2—, wherein Y1 is O, N or S;
• x is an integer of 1 or 2, wherein x is 1 when R2, R3 or R4 is bound to an unsaturated carbon atom and x is 2 when R2, R3 or R4 is bonded to a saturated carbon atom;
• R2 is H, lower alkyl, halogen, hydroxy or lower alkoxy, or oxo;
• R3 and R4 are, each, H, lower alkyl, hydroxy, lower alkoxy, or phenyl or, together, are —(C(R2)x)z—;
• —Y1(C(R2)x)z′—;
• —Y1(C(R2)x)y Y1—;
• —(C(R2)x)—Y1—(C(R2)x)—;
• —(C(R2)x)—Y1—(C(R2)x)—(C(R2)x)— and —Y1—(C(R2)x)—Y1—(C(R2)x)— wherein z is an integer of from 3 to 5, z′ is an integer of from 2 to 4 and x and y are as defined above, and further either end of each of these divalent moieties optionally attach at either R3 or R4 to form the condensed ring structure
• and the ring thus formed is totally unsaturated, partially unsaturated, or totally saturated provided that a ring carbon has no more than 4 valences, nitrogen no more than three and O and S have no more than two;
• or
• wherein W is a bicyclic radical selected from the group consisting of
• wherein R5, R6, R7 and R8 are selected from the group consisting of H and lower alkyl provided that at least one of R5 and R6 or R6 and R7 are OC(R9)C(R9)N(R) to form a condensed ring with
• wherein R9 is H, lower alkyl or oxo and
• wherein R10 is H, lower alkyl, phenyl or lower alkyl substituted phenyl, and Z is O or NH to treat muscle spasticity, pain, neurodegenerative diseases, spinal ischemia and stroke, memory and cognition deficits, attention deficit disorder, psychoses, anxiety, depression, hypertension, congestive heart failure, cardiac ischemia or nasal congestion wherein the active compound has the biological property that the compound is a selective agonist of α2B or α2B/α2C receptor subtype(s), said selectivity being measured in an assay using cells that naturally express the individual α2 subtypes or have had one of the subtypes introduced, the receptors being human or from a species that has been shown to have a similar pharmacology, in which assay the efficacy relative to brimonidine of the active compound at the α2B or the α2C receptor subtype is measured to be at least 0.3 greater than the efficacy relative to brimonidine of the active compound at the α2A receptor subtype and its efficacy at the α2A receptor is ≦0.4, and/or the active compound is at least approximately 10 times more potent at the α2B or α2C receptor subtypes than at the α2A receptor subtype.